Lung endothelial cells (ECs) are essential for maintaining organ function and homeostasis. Despite sharing some common features with ECs from organ systems, lung ECs exhibit significant heterogeneity in morphology, function, and gene expression. This heterogeneity is increasingly recognized as a key contributor to the development of pulmonary diseases like pulmonary hypertension (PH). In this mini-review, we explore the evolving understanding of lung EC heterogeneity, particularly through the lens of single-cell RNA sequencing (scRNA-seq) technologies. These advances have provided unprecedented insights into the diverse EC subpopulations, their specific roles, and the disturbances in their homeostatic functions that contribute to PH pathogenesis. In particular, these studies identified novel and functionally distinct cell types such as aerocytes and general capillary ECs that are critical for maintaining lung function in health and disease. In addition, multiple novel pathways and mechanisms have been identified that contribute to aberrant pulmonary vascular remodeling in PH. Emerging techniques like single-nucleus RNA sequencing and spatial transcriptomics have further pushed the field forward by discovering novel disease mediators. As research continues to leverage these advanced techniques, the field is poised to uncover novel EC subtypes and disease mechanisms, paving the way for new therapeutic targets in PH and other lung diseases.

The formation and progression of microvascular thrombosis are critical mechanisms underlying many vascular-related diseases. Therefore, replicating the microvascular blood flow environment in vitro and investigating the mechanisms of microvascular thrombosis formation are highly significant. In recent years, microfluidic chip technology has been extensively applied in in vitro research for its capability to systematically and comprehensively replicate the complex processes of microvascular thrombosis in laboratory settings. This review systematically examines the development and applications of microfluidic chip technology in microvascular thrombosis research. It begins with a brief summary of the technical features of microfluidic chip technology, followed by a detailed discussion of its applications in constructing in vitro microvascular models, investigating thrombosis mechanisms, and evaluating antithrombotic drug efficacy. Finally, the review summarizes the current research progress and discusses potential directions for future development. This review also systematically explains the breakthrough contribution of microfluidic chips from the perspective of engineering bionics and provides new insights for the pathological research and clinical management of microvascular thrombosis: constructing a high-precision physiological simulation system through bionic topology design and dynamic fluid regulation to achieve high-precision reconstruction of vascular dynamic microenvironment; based on the systems-level dynamics analysis, the dynamic evolution law of multi-factor synergy in the process of thrombosis is revealed; construct a drug-response evaluation system and establish a transformation bridge from micro-mechanism to clinical intervention. In summary, this review is expected to accelerate the development of targeted therapies and diagnostic tools for microvascular thrombosis.

Interfaces between distinct tissues or between tissues and environments are common in multicellular organisms. The evolution and stability of these interfaces are essential for tissue development, and their dysfunction can lead to diseases such as cancer. Mounting efforts, either theoretical or experimental, have been devoted to uncovering the morphodynamics of tissue interfaces. Here, we review the recent progress of studies on interface morphodynamics. The regulatory mechanisms governing interface evolution are dissected, with a focus on adhesion, cortical tension, cell activity, extracellular matrix, and microenvironment. We examine the methodologies used to study morphodynamics, emphasizing the characteristics of experimental techniques and theoretical models. Finally, we explore the broader implications of interface morphodynamics in tissue morphogenesis and diseases, offering a comprehensive perspective on this rapidly developing field.

COVID-19 is a disease that affects people globally. Beyond affecting the respiratory system, COVID-19 patients are at an elevated risk for both venous and arterial thrombosis. This heightened risk contributes to an increased probability of acute complications, including acute myocardial infarction (AMI) and acute ischemic stroke (AIS). Given the unclear relationship between COVID-19, AMI, and AIS, it is crucial to gain a deeper understanding of their associations and potential molecular mechanisms. This study aims to utilize bioinformatics to analyze gene expression data, identify potential therapeutic targets and biomarkers, and explore the role of immune cells in the disease.

This study employed three Gene Expression Omnibus (GEO) datasets for analysis, which included data on COVID-19, AMI and AIS. We performed enrichment analysis on the co-DEGs for these three diseases to clarify gene pathways and functions, and also examined the relationship between co-DEGs and immune infiltration. Machine learning techniques and protein-protein interaction networks (PPI) were used to identify hub genes within the co-DEGs. Finally, we employed a dual validation strategy integrating independent GEO datasets and in vitro experiments with human blood samples to comprehensively assess the reliability of our experimental findings.

We identified 88 co-DEGs associated with COVID-19, AMI and AIS. Enrichment analysis results indicated that co-DEGs were significantly enriched in immune inflammatory responses related to leukocytes and neutrophils. Immune infiltration analysis revealed significant differences in immune cell populations between the disease group and the normal group. Finally, genes selected through machine learning methods included: CLEC4E, S100A12, and IL1R2. Based on the PPI network, the top ten most influential DEGs were identified as MMP9, TLR2, TLR4, ITGAM, S100A12, FCGR1A, CD163, FCER1G, FPR2, and CLEC4D. The integration of the protein-protein interaction (PPI) network with machine learning techniques facilitated the identification of S100A12 as a potential common biomarker for early diagnosis and a therapeutic target for all three diseases. Ultimately, validation of S100A12 showed that it was consistent with our experimental results, confirming its reliability as a biomarker. Moreover, it demonstrated good diagnostic performance for the three diseases.

We employed bioinformatics methods and machine learning to investigate common diagnostic biomarkers and immune infiltration characteristics of COVID-19, AMI and AIS. Functional and pathway analyses indicated that the co-DEGs were primarily enriched in immune inflammatory responses related to leukocytes and neutrophils. Through two machine learning approaches and the PPI network, and subsequent validation and evaluation, we identified S100A12 as a potential common therapeutic target and biomarker related to immune response that may influence these three diseases.

Coronavirus disease identified in 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2, had a global impact on human health and the economy. The aim of this study was to quantify cytokines, chemokines, and acute phase proteins in the plasma of patients with COVID-19 to elucidate potential biomarkers to inform prognostic and treatment decisions. Clustering analysis using the K-prototypes method identified underlying biological patterns in patients with COVID-19. The penalized multinomial logistic regression analysis identified two comorbidities (hypertension, congestive heart failure) and thirteen analytes as potential risk factors for COVID-19 progression with 88.2% accuracy. Based on a patient's age, high concentrations of interleukin (IL)-6, monocyte chemoattractant protein-1, and pentraxin 3 were important biomarkers for lethal COVID-19. Decreased concentrations of interferon gamma-induced protein-10, IL-10, and soluble tumor necrosis factor receptor I were found to be associated with mild COVID-19, while increasing concentrations of these analytes could be used to predict COVID-19 severity.

Deep vein thrombosis is an acute medical condition, and the molecular basis of this etiology will be crucial in the discovery of more advanced therapies. This review has focused at the Notch signaling pathway, which plays a significant role in different physiological activities such as homeostasis, development, and disease. Also, reveal macrophage function in inflammation and thrombosis in depth, with a focus on their polarization and interaction with the endothelium during thrombosis. In this context, some essential cellular and molecular mechanisms relevant to thrombus pathogenesis, DVT aetiology and risk factors, as well as elements and composition of the Notch pathway, are covered in the end, with a focus on elements that distinguish canonical from non-canonical signaling pathways and their biological relevance to macrophages. Notch signaling has been shown to influence macrophage activation and polarization, influencing their function in thrombosis breakdown and resolution. This interplay between Notch signaling and macrophages may reveal possible treatment targets for DVT. Discuss the physiological role of Notch signaling in vascular biology, as well as how it contributes to thrombosis. The difficulties in implementing these discoveries in clinical practice are discussed, along with the status of ongoing clinical trials and experimental investigations focussing on macrophage-directed treatments and Notch inhibitors. These molecular insights synthesis provides a basis for the creation of novel strategies for the efficient management of DVT.

Thrombosis is a serious health hazard, which has been paid more and more attention.Okra polysaccharide (OP) is a biologically active substance extracted from okra which exhibits anti-inflammation and anti-oxidative properties. Nevertheless, the effect of OP on thrombosis is still unknown. In this study, we determined whether OP can suppress carrageenan-induced mice thrombosis and its involved mechanism.

Twenty-four BALB/c mice were assigned to four groups randomly (6 mice/group): Ctrl, Model, OP low lose (OP-L, 200 mg/kg body weight), and OP high lose (OP-H,400 mg/kg body weight) were administered via intragastric administration for 9 days. Tails were photographed before collecting for H&E and Masson staining. Liver and lung tissues were collected for H&E staining, RT-qPCR, Western blot and GSH content detection. Injury or dysfunction of endothelial cells (ECs) was assessed using RT-qPCR, Western blot and cell adhesion assays.

OP can effectively improve carrageenan-induced thrombosis in tissues of mice (tail, liver, and lung) in vivo. In addition, OP inhibited inflammation by suppressing the toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway and reduced oxidative damage by elevating the level of GSH and antioxidant enzyme in liver and lung tissues. In vitro, OP inhibited thrombin-induced human platelet clots retraction, and decreased lipopolysaccharide (LPS)-activated adhesion of THP-1 monocytes to human umbilical vein endothelial cells(HUVECs) by suppressing intercellular adhesion molecule-1 (ICAM-1) level.

In conclusion, OP can inhibit thrombosis in mouse model by regulating inflammation and oxidative stress, which suggest that OP could act as a potential functional food for prevention of thrombus.

There is active crosstalk between tumor cells and the tumor microenvironment during metastatic progression, a process that is significantly affected by obesity, particularly in breast cancer. Here we analyze the impact of a high fat diet (HFD) on metastasis, focusing on the role of platelets in the formation of premetastatic niches (PMNs). We find that a HFD provokes pre-activation of platelets and endothelial cells, promoting the formation of PMNs in the lung. These niches are characterized by increased vascular leakiness, platelet activation and overexpression of fibronectin in both platelets and endothelial cells. A HFD promotes interactions between platelets, tumor cells and endothelial cells within PMNs, enhancing tumor cell homing and metastasis. Importantly, therapeutic interventions like anti-platelet antibody administration or a dietary switch reduce metastatic cell homing and outgrowth. Moreover, blocking fibronectin reduces the interaction of tumor cells with endothelial cells. Importantly, when coagulation parameters prior to neoadjuvant treatment are considered, triple negative breast cancer (TNBC) female patients with reduced Partial Thromboplastin time (aPTT) had a significantly shorter time to relapse. These findings highlight how diet and platelet activation in pre-metastatic niches affect tumor cell homing and metastasis, suggesting potential therapeutic interventions and prognostic markers for TNBC patients.

Early failure of a pancreatic allograft due to complete thrombosis has an incidence of approximately 10% and is the main cause of comorbidity in pancreas transplantation. Although several risk factors have been identified, the exact mechanisms leading to this serious complication are still unclear. In this review, we define the roles of the individual components involved during sterile immunothrombosis-namely endothelial cells, platelets, and innate immune cells. Further, we review the published evidence linking the main risk factors for pancreatic thrombosis to cellular activation and vascular modifications. We also explore the unique features of the pancreas itself: the vessel endothelium, specific vascularization, and relationship to other organs-notably the spleen and adipose tissue. Finally, we summarize the therapeutic possibilities for the prevention of pancreatic thrombosis depending on the different mechanisms such as anticoagulation, anti-inflammatory molecules, endothelium protectors, antagonism of damage-associated molecular patterns, and use of machine perfusion.

Chronic inflammation is a pivotal driver in the progression of atherosclerosis, significantly contributing to the burden of cardiovascular disease (CVD). Patients with chronic inflammatory diseases, such as inflammatory bowel diseases (IBDs) (e.g., ulcerative colitis and Crohn's disease), rheumatological disorders, as well as individuals with auto-immune diseases (such as systemic lupus erythematosus), present a higher risk of major adverse cardiac events (MACEs). Despite their elevated CVD risk, these populations remain underrepresented in cardiovascular research, leading to a critical underestimation of their cardiovascular risk (CVR) in clinical practice. Furthermore, even recent CVR scores poorly predict the risk of events in these specific populations. This narrative review examines the physiopathological mechanisms linking chronic inflammation, immunomodulation, atherosclerosis, thrombosis and cardiovascular events. We review data from epidemiological studies and clinical trials to explore the potential cardiovascular benefits of anti-inflammatory and immunomodulatory therapies. Despite existing evidence, significant gaps in knowledge remain. Future research is mandatory, focusing on innovative strategies for risk stratification and optimization, including lipidomics, proteomics, advanced inflammatory markers, microbiota profiling, and cardiovascular imaging. Addressing these unmet needs will enhance understanding of cardiovascular risk in chronic inflammatory diseases, enabling tailored interventions and better outcomes.

Acute kidney injury (AKI) is a clinical challenge characterized by elevated morbidity and a substantial impact on individual health and socioeconomic factors. A comprehensive examination of the molecular pathways behind AKI is essential for its prevention and management. In recent years, vigorous research in the domain of AKI has concentrated on pathophysiological characteristics, early identification, and therapeutic approaches across many aetiologies and highlighted the principal themes of oxidative stress, inflammatory response, apoptosis, necrosis, and immunological response. This review comprehensively reviewed the molecular mechanisms underlying AKI, including oxidative stress, inflammatory pathways, immune cell-mediated injury, activation of the renin-angiotensin-aldosterone (RAAS) system, mitochondrial damage and autophagy, apoptosis, necrosis, etc. Inflammatory pathways are involved in the injuries in all four structural components of the kidney. We also summarized therapeutic techniques and pharmacological agents associated with the aforementioned molecular pathways. This work aims to clarify the molecular mechanisms of AKI thoroughly, offer novel insights for further investigations of AKI, and facilitate the formulation of efficient therapeutic methods to avert the progression of AKI.

COVID-19, caused by the SARS-CoV-2 virus, is not only characterized by respiratory symptoms but is also associated with a wide range of systemic complications, including significant hematologic abnormalities. This is a comprehensive review of the current literature, using PubMed and Google Scholar, on the pathophysiology and incidence of thromboembolic events in COVID-19 patients and thromboprophylaxis. COVID-19 infection induces a prothrombotic state in patients through the dysregulation of the renin-angiotensin-aldosterone system (RAAS), endothelial dysfunction, elevated von Willebrand factor (vWF), and a dysregulated immune response involving the complement system and neutrophil extracellular traps (NETs). As a result, thromboembolic complications have emerged in COVID-19 cases, occurring more frequently in severe cases and hospitalized patients. These thrombotic events affect both venous and arterial circulation, with increased incidences of deep venous thrombosis (DVT), pulmonary embolism (PE), systemic arterial thrombosis, and myocardial infarction (MI). While DVT and PE are more common, the literature highlights the potential lethal consequences of arterial thromboembolism (ATE). This review also briefly examines the ongoing discussions regarding the use of anticoagulants for the prevention of thrombotic events in COVID-19 patients. While theoretically promising, current studies have yielded varied outcomes: Some suggest potential benefits, whereas others report an increased risk of bleeding events among hospitalized patients. Therefore, further large-scale studies are needed to assess the efficacy and safety of anticoagulants for thromboprophylaxis in COVID-19 patients.

Vascular endothelial cells (VECs) play a crucial role in the development and maintenance of vascular biology specific to the tissue types. Molecular signature-based labeling and imaging of VECs help researchers understand potential mechanisms linking VECs to disease pathology, serving as valuable biomarkers in clinical settings and trials. Labeling techniques involve selectively tagging or marking VECs for visualization. Immunolabeled employs antibodies that specifically bind to VECs markers, while fluorescent tracers or dyes can directly label VECs for imaging. Some techniques use specific carbohydrate residues on cell surface, while others employ endothelial-specific promoters to express fluorescent proteins. Additionally, VEC can be labeled with contrast agents, radiolabeled tracers, and nanoparticles. The choice of labeling technique depends on study context, including whether it involves animal models, in vitro cell cultures, or clinical applications. Herein, we discussed the various labeling methods utilized to label VECs and the techniques to visualize them.

Vascular hypo-fibrinolysis is a historically underappreciated and understudied aspect of venous thromboembolism (VTE). This paper describes the development of a micro-clot dissolution assay for quantifying the fibrinolytic capacity of endothelial cells - a key driver of VTE development. This assay is enabled using aqueous two-phase systems (ATPS) to bioprint microscale fibrin clots over human umbilical vein endothelial cells (HUVECs). Importantly, these micro-clots are orders of magnitude smaller than conventional fibrin constructs and allow HUVEC-produced plasminogen activators to mediate visually quantifiable fibrinolysis. Using live-cell time-lapse imaging, micro-clot dissolution by HUVECs is tracked, and fibrinolysis kinetics are quantified. The sensitivity of cell-driven fibrinolysis to various stimuli is rapidly tested. The physiological relevance of this convenient high-throughput assay is illustrated through treatments with lipopolysaccharide (LPS) and rosuvastatin that elicit anti- and pro-fibrinolytic responses, respectively. Furthermore, treatment with baricitinib, an anti-inflammatory therapeutic found to increase cardiovascular risks after market approval, provokes an anti-fibrinolytic response - which highlights the potential role of endothelial cells in increasing VTE risk for patients receiving this drug. This endothelial cell fibrinolysis assay provides a high-throughput and versatile drug testing platform - potentially allowing for early preclinical identification of therapeutics that may beneficially enhance or adversely impair endothelial fibrinolysis.

In recent years, the introduction of sodium-glucose transporter-2 inhibitors (SGLT2is) marked a significant advancement in the treatment of cardiovascular disease (CVD). Beyond their known effects on glycemic control and lipid profile, SGLT2is demonstrate notable benefits for cardiovascular morbidity and mortality, regardless of diabetic status. These agents are currently recommended as first-line therapies in patients with heart failure, both with reduced and preserved ejection fraction, as they improve symptoms and reduce the risk of hospitalization. While several studies have demonstrated that SGLT2is can reduce the incidence of major adverse cardiovascular events (MACEs), the true impact of these agents on atherosclerosis progression and myocardial ischemia remains to be fully understood. A global beneficial effect related to improved glycemic and lipid control could be hypothesized, even though substantial evidence shows a direct impact on molecular pathways that enhance endothelial function, exhibit anti-inflammatory properties, and provide myocardial protection. In this context, this narrative review summarizes the current knowledge regarding these novel anti-diabetic drugs in preventing and treating myocardial ischemia, aiming to define an additional area of application beyond glycemic control and heart failure.

Frostbite injury refers to cold tissue injury which typically affects the peripheral areas of the body, and is associated with limb loss and high rates of morbidity. Historically, treatment options have been limited to supportive care, leading to suboptimal outcomes for affected patients. The pathophysiology of frostbite injury has been understood in recent years to share similarity with that of cold ischemia-reperfusion injury as seen in solid organ transplantation, of which mitochondria play an important contributing role. The present study investigated whether AP39, a novel mitochondria-targeted slow-releasing hydrogen sulfide donor, applied topically in a vehicle cream at 200 nM or 1 µM could mitigate frostbite injury and promote wound healing in mice. Frostbite injury was induced continuously for 3 min on the dorsal skin of C57BL/6 mice (Mus musculus) using magnets frozen on dry ice (-80 °C). AP39, delivered via a vehicle cream, was used daily to treat frostbite injury until animals were euthanized on day 15 after induction of frostbite injury. Wound tissues were stained with hematoxylin and eosin along with immunofluorescence staining with cleaved caspase-3, CD31, KI-67, CD163, fibronectin and cytokeratin. While 200 nM AP39 improved granulation tissue maturation (p < 0.001), angiogenesis (p < 0.01) and cell proliferation (p < 0.001) compared to vehicle control, 1 µM AP39 further increased granulation tissue formation compared to other frostbite groups (p < 0.001). Thus, AP39 promoted frostbite wound healing, and therefore could be considered as a treatment option for patients with frostbite injury.

Blood coagulation is a highly regulated injury response that features polymerization of fibrin fibers to prevent the passage of blood from a damaged vascular endothelium. A growing body of research seeks to monitor coagulation in microfluidic systems but fails to capture coagulation as a response to disruption of the vascular endothelium. Here we present a device that allows compression injury of a defined segment of a microfluidic vascular endothelium and the assessment of coagulation at the injury site. This pressure injury-on-a-chip (PINCH) device allows visualization of coagulation as the accumulation of fluorescent fibrin at injury sites. Quantification of fluorescent fibrin levels upstream of and at injury sites confirm that pre-treating vascular endothelium with fluid shear stress helps capture coagulation as an injury response. We leverage the PINCH devices to demonstrate the limited coagulation response of type A hemophiliacs and evaluate the performance of hemostatic microparticles and fibrinolytic nanoparticles. Our findings and the straightforward fabrication of the PINCH devices make it a promising choice for additional screening of hemostatic therapeutics.

The anti-atherosclerotic effects of high-density lipoprotein (HDL) prevent the onset of cerebral infarction and provide cerebroprotective effects against ischemia-reperfusion injury. These inhibitory effects have been attributed to its antioxidant, anti-inflammatory, and antithrombotic properties. However, pharmacotherapeutic strategies to clinically realize these effects have not been demonstrated. Therefore, we aimed to develop paraoxonase 1 (PON1), a hydrolytic enzyme associated with HDL that exhibits antioxidant and anti-inflammatory effects, as a novel therapeutic agent against ischemia-reperfusion injury in cerebral infarction. We established a method to extract PON1 from human plasma with high purity and recovery while maintaining its activity. The purified PON1 exhibited antioxidant activity against human-derived LDL and HDL. Furthermore, PON1 actively suppressed the oxidation chain reaction by hydrolyzing lipid peroxides. The HDL-binding ability of PON1 was evaluated based on its activity in fractionated HDL from mice administered PON1 intravenously, which showed that most intravenously administered PON1 specifically bound to HDL. The cerebroprotective effect of intravenously administered PON1 was assessed using a mouse middle cerebral artery ischemia-reperfusion model by measuring infarct volume, long-term neurological scores, and walking time on a rotarod. Administration of PON1 after reperfusion reduced infarct volume 24 h after ischemia-reperfusion. Additionally, daily administration of PON1 for three days significantly improved neurological scores and walking time by approximately one month. Analysis of gene arrays in brain tissue indicated that PON1 suppresses biological functions and pathways associated with oxidative stress, inflammation, vascular dysfunction, thrombosis, and fibrosis. PON1 enhances the cerebroprotective effects of HDL and is a potential candidate for acute stroke therapy.

Inflammation drives cardiovascular disease in rheumatoid arthritis (RA). Treatment with tofacitinib, a JAK1/JAK3 inhibitor, is associated with increased cardiovascular events in patients with RA. Here, we determined its effects on cytokine production during interactions between immune cells at the synovial and vascular levels and its impact on endothelial activation and coagulation during inflammation.

Activated human peripheral blood mononuclear cells (PBMCs) were cocultured with RA synoviocytes or endothelial cells (ECs) mimicking the cellular interactions in synovium and vessels responsible for cytokine production. A dose-response of tofacitinib was tested on interferon γ, interleukin (IL) 17A, IL-10, IL-6, and IL-1β, and cytokine production was measured by enzyme-linked immunosorbent assay at 48 hours. Endothelial activation was induced with IL-17A and tumor necrosis factor (TNF) or on contact with PBMCs. Shortly after tofacitinib treatment, the expression of EC activation markers, specifically IL-6, IL-8, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin, and of coagulation, including tissue factor and thrombomodulin, was assessed by real-time polymerase chain reaction.

Tofacitinib differentially inhibited production of IFNɣ, IL-17A, and IL-10 from PBMC cocultures with RA synoviocytes or ECs (all P < 0.001). In cocultures with ECs, tofacitinib reduced further IL-6 and IL-8 production (both P < 0.001). In ECs activated by TNF/IL-17A or indirectly via contact with activated PBMCs, tofacitinib decreased IL-6 upregulation but not that of IL-8, E-selectin, or tissue factor. Thrombomodulin was significantly decreased. VCAM-1 was greatly induced with a higher dose of tofacitinib in ECs incubated directly with added inflammatory cytokines (P < 0.05) or released by interaction with activated PBMCs (P < 0.001).

Tofacitinib inhibits synovium and vascular inflammation but fails to prevent the prothrombotic effects of inflammatory cytokines on ECs.

The heterogeneity of thrombi in terms of composition, structure, and blood rheology parameters presents a challenge for effective thrombus-targeting drug delivery. To address this, a self-adaptive nano-delivery system, termed D-PLT, is developed. It consists of platelet membrane-cloaked deformable mesoporous organic silicon dioxide nanocomposite, enabling it to respond to the challenge of the heterogeneity of thrombi in arteries and veins. The system exhibits progressive targeting, with the ability to target arterial and venous thrombosis and damaged blood vessels. D-PLT physically matches the pore structure of the thrombus by undergoing varied deformation, leading to advanced targeting and enrichment of arterial and venous thrombus. When co-loaded with the thrombolytic drug urokinase (UK) and the endothelium-protecting agent atorvastatin calcium (AT), the system improves rapid vascular opening of arterial and venous thrombosis in 90 min and provides up to 7 days of durable thrombolysis and recovery from endothelial dysfunction in vivo. This self-adaptive delivery system offers a promising strategy to overcome thrombus heterogeneity.

Introduction: Deep vein thrombosis (DVT) is a major cause of cardiovascular disease-related deaths worldwide and is considered a thrombotic inflammatory disorder. IL-1β, as a key promoter of venous thrombus inflammation, is a potential target for DVT treatment. Constructing a nanocarrier system for intracellular delivery of siIL-1β to silence IL-1β may be an effective strategy for alleviating DVT. Methods: ELISA was used to detect the expression levels of IL-1β and t-PA in the serum of DVT patients and healthy individuals. In vitro, HUVEC cells were treated with IL-1β, and changes in VWF and t-PA expression levels were assessed. PBAE/MCM-41@siIL-1β (PM@siIL-1β) nano-complexes were synthesized, the characterization and biocompatibility of PM@siIL-1β were evaluated. A rat hind limb DVT model was established, and PM@siIL-1β was used to treat DVT rats. Morphology of the inferior vena cava, endothelial cell count, IL-1β, vWF, and t-PA levels, as well as changes in the p38 MAPK and NF-κB pathways, were examined in the different groups. Results: IL-1β and t-PA were highly expressed in DVT patients, and IL-1β treatment induced a decrease in VWF levels and an increase in t-PA levels in HUVEC cells. The synthesized PM@siIL-1β exhibited spherical shape, good stability, high encapsulation efficiency, and high drug loading capacity, with excellent biocompatibility. In the DVT model rats, the inferior vena cava was filled with blood clots, endothelial cells increased, IL-1β and VWF levels significantly increased, while t-PA levels were significantly downregulated. Treatment with PM@siIL-1β resulted in reduced thrombus formation, decreased endothelial cell count, and reversal of IL-1β, VWF, and t-PA levels. Furthermore, PM@siIL-1β treatment significantly inhibited p38 phosphorylation and upregulation of NF-κB expression in the DVT model group. Conclusion: IL-1β can be considered a therapeutic target for suppressing DVT inflammation. The synthesized PM@siIL-1β achieved efficient delivery and gene silencing of siIL-1β, demonstrating good therapeutic effects on rat hind limb DVT, including anti-thrombotic and anti-inflammatory effects, potentially mediated through the p38 MAPK and NF-κB pathways.

Vitamin D (VD) is a vital lipophilic secosteroid hormone known for its essential role in maintaining skeletal health and regulating calcium and phosphate metabolism. Recent evidence has begun to illuminate its significance beyond bone health, particularly in relation to thrombosis-a condition characterized by blood clot formation within the vascular system that can lead to serious cardiovascular events such as myocardial infarction and stroke. VD deficiency, defined as a plasma 25-hydroxyVD level below 25 nmol/L, affects a substantial portion of the global population, with prevalence rates ranging from 8% to 18%. This study systematically explores the relationships between VD levels and the risk of thrombosis, investigating the underlying mechanisms including VD's anticoagulant properties, influence on inflammatory pathways, and interactions with endothelial cells. Epidemiological data suggest that low serum levels of VD correlate with an increased risk of venous thromboembolism (VTE), although the reported findings remain inconsistent. Mechanisms that potentially link VD to thrombotic risk include modulation of thrombomodulin and tissue factor expression, as well as enhancement of anti-inflammatory cytokines. Given the prevalence of VD insufficiency, particularly among populations with limited exposure to sunlight, this research highlights the urgent need for strategies to increase VD levels through dietary modifications and supplementation in order to prevent thrombotic events.

To explore whether red blood cell distribution width-albumin ratio (RAR) is relevant to in-hospital mortality among abdominal aortic aneurysm (AAA). This is a retrospective study retrieving data from the MIMIC-IV database. Patients were divided into survivor or non-survivor groups by the in-hospital mortality. Receiver operating characteristic curve analysis, logistic regression models, subgroup analysis, interaction analysis, and restricted cubic spline analysis were conducted to analyze the correlation between RAR and in-hospital mortality. Then, we divided patients into 2 groups by an optimal cutoff value of RAR to identify the factors independently linked to RAR. Following this, the mediation analysis was conducted to reveal the potential regulatory path. Finally, we assessed the clinical value of RAR in secondary outcomes containing length of hospital stay, intensive care unit (ICU) admission, and ICU stay. Totally 770 participants with AAA were enrolled: 722 survivors and 48 non-survivors. Higher RAR was observed in the non-survivor group and its level performed satisfactorily in predicting in-hospital mortality. AAA patients were more likely to die during in-hospital with the increase of RAR (P < .05) and this linear correlation was revealed by restricted cubic spline (P non-linear > .05). Additionally, urea nitrogen and creatinine were independently related to RAR. RAR served as a mediator in the association of urea nitrogen/creatinine with in-hospital mortality. Finally, the length of hospital stay and ICU stay were longer in the RAR ≥ 4.658 group (P < .05). RAR is a potential risk predictor for in-hospital mortality in AAA patients. Further, RAR upregulation was significantly correlated with prolonged length of hospital stay and ICU stay.

Thrombosis, a leading cause of cardiovascular morbidity and mortality, involves the formation of blood clots within blood vessels. Current animal models and in vitro systems have limitations in recapitulating the complex human vasculature and hemodynamic conditions, limiting the research in understanding the mechanisms of thrombosis. Bioprinting has emerged as a promising approach to construct biomimetic vascular models that closely mimic the structural and mechanical properties of native blood vessels. This review discusses the key considerations for designing bioprinted vascular conduits for thrombosis studies, including the incorporation of key structural, biochemical and mechanical features, the selection of appropriate biomaterials and cell sources, and the challenges and future directions in the field. The advancements in bioprinting techniques, such as multi-material bioprinting and microfluidic integration, have enabled the development of physiologically relevant models of thrombosis. The future of bioprinted models of thrombosis lies in the integration of patient-specific data, real-time monitoring technologies, and advanced microfluidic platforms, paving the way for personalized medicine and targeted interventions. As the field of bioprinting continues to evolve, these advanced vascular models are expected to play an increasingly important role in unraveling the complexities of thrombosis and improving patient outcomes. The continued advancements in bioprinting technologies and the collaboration between researchers from various disciplines hold great promise for revolutionizing the field of thrombosis research.

This study aimed to evaluate the clot-lysing and membrane stabilizing capacities of ascorbic acid (AA) using in vitro and in silico methods. For this, we used in vitro clot lysis and hemolyzing tests to check the anti-atherothrombosis and membrane-stabilizing properties of AA, respectively. Additionally, molecular docking studies were performed to investigate AA's interactions with cyclooxygenase-1 (COX-1) and plasminogen enzymes. Findings suggest that AA exhibited a concentration-dependent effect, with 43.95 ± 1.27 % clot lysis and 64.46 ± 0.01 % membrane stabilization at 100 µg/mL. The IC50 values for clot lysis and membrane stabilization were 215.19 ± 1.09 and 57.21 ± 2.11 µg/mL, respectively. In silico analysis showed strong binding affinities of AA with COX-1 (-6.2 kcal/mol) and plasminogen (-5.8 kcal/mol), supporting its observed clot lysis and membrane protection activities. Taken together, AA showed moderate clot-lysing and robust membrane-stabilizing effects, which may be due to its strong antioxidant and anti-inflammatory properties. AA might be a good therapeutic agent for atherothrombosis and membrane damage, highlighting the need for further investigation into its underlying molecular mechanisms and potential clinical applications. AA shows promising clot-lysing and membrane-stabilizing effects, highlighting its therapeutic potential for atherothrombosis and membrane damage.

We carried out a retrospective observational investigation to explore the association of endotheliopathy with coagulofibrinolytic reactions and the progression of disseminated intravascular coagulation (DIC) in adult trauma patients. We measured syndecan-1 (SDC-1), an indicator of endotheliopathy, and biomarkers of coagulofibrinolysis in 100 trauma patients immediately transferred to Ehime University Hospital. We evaluated the correlations between the coagulofibrinolytic parameters and SDC-1. We also investigated the association between SDC-1 elevations and the development of DIC, and determined the discriminators of DIC development. The median SDC-1 concentration was 82.7 (43.5-178.1) ng/mL. DIC developed in 16 patients (16.0%), and SDC-1 concentrations were significantly higher in DIC patients than in non-DIC patients (218.8 [134.5-798.2] ng/mL vs. 67.2 [39.6-114.5] ng/mL, p < 0.001). Receiver operating characteristic curve analysis revealed that the circulating SDC-1 level effectively predicted the progression of DIC, with an area under the curve of 0.862 (95% confidence interval [CI], 0.789-0.936). The optimal cut-off value was determined to be 92.5 ng/mL, yielding a sensitivity of 100.0% and a specificity of 67.8% (p < 0.001). A simple logistic regression analysis showed that a circulating SDC-1 concentration of > 92.5 ng/mL was significantly correlated with DIC progression (odds ratio [OR], 31.67; 95%CI: 3.97-252.31, p = 0.001). Many coagulofibrinolytic parameters were significantly correlated with SDC-1. Estimating the discriminators of DIC development by the least absolute shrinkage and selection operator (LASSO) and elastic-net regression analysis identified markers of coagulofibrinolytic activation, such as thrombin-antithrombin complex (TAT) and tissue plasminogen activator (tPA). A multivariate logistic regression model using TAT, tPA, and SDC-1 demonstrated that TAT and tPA, but not SDC-1, were independent factors predicting the development of DIC (TAT per 10 µg/L: OR, 1.14, 95%CI: 1.05-1.24, p = 0.003; tPA per 100pg/mL: OR, 1.03, 95%CI: 1.01-1.05, p = 0.003; SDC-1 per 10ng/mL: OR, 1.00, 95%CI: 0.99-1.01, p = 0.973). Mediation analysis showed that SDC-1 elevation was predominantly associated with the development of DIC indirectly through the increase in TAT (proportion mediated = 96.1%, p < 0.001), while there was no significant indirect effect of SDC-1 elevation on the role of TAT elevation in DIC development was observed (p = 0.340). The primary pathogenesis of DIC in the acute phase of trauma is likely driven by coagulofibrinolytic activation. Endotheliopathy, as reflected by elevated circulating levels of SDC-1, is strongly associated with coagulofibrinolytic responses. Although endotheliopathy may contribute to the early development of DIC through coagulation activation, its role appears to be limited.

The global increase in cardiovascular diseases has resulted in an augmented development of artificial small-caliber vascular grafts used in bypass graft surgeries, such as coronary and distal artery bypass graft surgeries. However, no consensus exists regarding the best method for creating vascular grafts. Poly-ε-caprolactone (PCL) is a biocompatible and biodegradable material that has been widely studied as a scaffold for tissue regeneration, inclusive of vascular grafts. In this study, a vascular graft was created from a PCL nanofiber sheet (PCL graft), and the performance thereof was examined using a rat abdominal aortic implantation model.

The PCL nanofiber sheets were created using an electrospinning machine. These nanofiber sheets were rolled up. Glue was applied between layers using a PCL solution to create a PCL nanofiber vascular graft, with an inner diameter of 1 mm. PCL grafts with 7 mm length were implanted into the abdominal aorta of rats. Thereafter, the patency was determined by pulsating blood flow from the hemiresection site of the distal aorta of the graft anastomosis, and endothelialization was examined using hematoxylin and eosin and immunofluorescent staining methods.

The patency rate of the PCL graft at 2 weeks was 57.1% (12 of 21 cases), which is not satisfactory as a small-caliber vascular graft. Patent cases, however, revealed a CD31-positive endothelial cell layer in the inner lumen and autologous cell infiltration into the scaffold, indicating autologous vessel-like regeneration. By contrast, the occluded cases showed disassembly of the nanofiber layers; and the inner layers folded into the middle of the lumen. This observation suggested that the disassembled inner layer of the PCL graft disturbed the blood flow and triggered occlusion.

PCL grafts can exhibit autologous vessel-like regeneration; nonetheless, regarding patency, grafts made from rolled-up PCL nanofiber sheets have structural weaknesses. Further improvements are required to achieve a long-term and high patency rate for PCL grafts.

Endothelial dysfunction is an early predictor of atherosclerosis and cardiovascular disease. Flow-mediated dilation (FMD) is the gold standard to assess endothelial function in humans. FMD reproducibility has been mainly assessed in the brachial artery (BA) with limited research in lower limb arteries. The purpose of this study was to compare FMD reproducibility in the upper limb BA and lower limb superficial femoral artery (SFA) in young healthy adults.Fifteen young healthy adults (nine males; six females) underwent FMD, resting diameter, velocity, and shear rate measurements on three occasions to determine intra-and inter-day reproducibility in both BA and SFA, assessed by coefficient of variation (CV), intraclass correlation coefficient (ICC), and Bland-Altman plots.BA FMD CVs (intra-day: 4.2%; inter-day: 8.7%) and ICCs (intra-day: 0.967; inter-day: 0.903) indicated excellent reproducibility and reliability, while for SFA FMD, both CVs (intra-day: 11.6%; inter-day: 26.7%) and ICCs (intra-day: 0.898; inter-day: 0.651) showed good/moderate reproducibility and reliability. BA FMD was significantly more reproducible than SFA FMD (p < 0.05). Diameter reproducibility was excellent and similar between arteries, while resting velocity and shear rate have lower reproducibility in the BA compared to SFA. Bland-Altman plots displayed no proportional and fixed bias between measurements.In summary, SFA FMD is less reproducible than BA FMD, with identical volume of ultrasound training. Given the increasing interest in using SFA FMD to test the efficacy of interventions targeting lower limb's vascular health and as a potential biomarker for peripheral arterial disease risk, future studies should ensure higher levels of training for adequate reproducibility.

The clinical efficacy of tissue plasminogen activator (tPA) is limited by its lack of specific delivery, requiring large therapeutic doses that increase the risk of intracerebral hemorrhage, bleeding at the surgical site, and patient mortality after angioplasty. To address these limitations, this study aimed to develop a chitosan polysulfate (CsPs)-coated liposomal formulation for the sustained release of tPA. The CsPs-coated liposomes containing tPA (Liposome-tPA/CsPs) were fabricated using the thin-film hydration technique and their properties were compared to tPA-encapsulated nanoliposomes without a coating layer (Liposome-tPA). Liposome-tPA/CsPs showed a quasi-spherical morphology with a hydrodynamic diameter of 110 nm, while Liposome-tPA had a diameter of 80 nm. The thermal analysis showed that the degradation temperature and glass transition temperature (Tg) of Liposome-tPA/CsPs were higher than that of tPA alone, indicating improved temperature stability. The in vitro release study demonstrated a slow and sustained release of tPA from the Liposome-tPA/CsPs, with a concentration of 0.02 mg/ml at 1 h and 0.23 mg/ml at 180 h. The CsPs coating layer enhanced the antibacterial and antioxidant activity of the nanoliposomes. Liposome-tPA/CsPs exhibited higher cell viability compared to Liposome-tPA. It also achieved a higher percentage of thrombolysis, with complete clot dissolution observed after 3 h of treatment. These findings suggest that the Liposome-tPA/CsPs can be a promising approach to overcome the limitations associated with the systemic administration of tPA, potentially enhancing its clinical efficacy while reducing the risk of adverse events.

Device-related thrombosis (DRT) occurs in up to 4% of patients undergoing left atrial appendage occlusion (LAAO) and is associated with substantial morbidity and mortality. However, its pathophysiology, predictors, and optimal management remain unclear.

This study aims to assess flow dynamic factors correlating to DRT.

A multicenter registry of patients who underwent LAAO and had pre- and post-computed tomography imaging was used. Patient-specific 3-dimensional digital models of the left atrium were created, and finite element simulations were performed to implant an LAAO device into each model in a position that matched the clinical deployment. Computational fluid dynamic simulations were performed to quantify the following flow dynamic parameters: time averaged wall shear stress, oscillatory shear index, and endothelial cell activation potential.

A total of 38 patients (19 with DRT and 19 without DRT) were included. Left atrium volumes and mitral valve areas were larger in the DRT cohort compared with controls. Patients with DRT had a significantly lower time averaged wall shear stress (1.76 ± 1.24 Pa vs 2.90 ± 2.70 Pa), a higher oscillatory shear index (0.19 ± 0.11 vs 0.17 ± 0.11), and a higher endothelial cell activation potential (0.23 ± 0.58 Pa-1 vs 0.17 ± 0.30 Pa-1) than the controls (P < 0.001 for all). Thrombus locations identified from in-vivo images correlated well with the flow dynamic parameters tested.

Flow dynamic parameters may be able to predict the risk of DRT after LAAO. Further investigation with a larger patient cohort and long-term follow-up is needed to assess the role of computational fluid dynamics in the risk stratification of patients considered for LAAO.

Discovered in late 2019, the SARS-CoV-2 coronavirus has caused the largest pandemic of the 21st century, claiming more than seven million lives. In most cases, the COVID-19 disease caused by the SARS-CoV-2 virus is relatively mild and affects only the upper respiratory tract; it most often manifests itself with fever, chills, cough, and sore throat, but also has less-common mild symptoms. In most cases, patients do not require hospitalization, and fully recover. However, in some cases, infection with the SARS-CoV-2 virus leads to the development of a severe form of COVID-19, which is characterized by the development of life-threatening complications affecting not only the lungs, but also other organs and systems. In particular, various forms of thrombotic complications are common among patients with a severe form of COVID-19. The mechanisms for the development of thrombotic complications in COVID-19 remain unclear. Accumulated data indicate that the pathogenesis of severe COVID-19 is based on disruptions in the functioning of various innate immune systems. The key role in the primary response to a viral infection is assigned to two systems. These are the pattern recognition receptors, primarily members of the toll-like receptor (TLR) family, and the complement system. Both systems are the first to engage in the fight against the virus and launch a whole range of mechanisms aimed at its rapid elimination. Normally, their joint activity leads to the destruction of the pathogen and recovery. However, disruptions in the functioning of these innate immune systems in COVID-19 can cause the development of an excessive inflammatory response that is dangerous for the body. In turn, excessive inflammation entails activation of and damage to the vascular endothelium, as well as the development of the hypercoagulable state observed in patients seriously ill with COVID-19. Activation of the endothelium and hypercoagulation lead to the development of thrombosis and, as a result, damage to organs and tissues. Immune-mediated thrombotic complications are termed "immunothrombosis". In this review, we discuss in detail the features of immunothrombosis associated with SARS-CoV-2 infection and its potential underlying mechanisms.

Therapeutic plasma exchange (TPE) is a widely used treatment for numerous diseases including pregnancy-related conditions. Our prior study on 20 early-onset preeclampsia patients undergoing TPE revealed a significant extension in pregnancy duration and reduced serum levels of sFlt-1, sFlt-1/PlGF, and sEndoglin. Here, we investigated the impact of TPE on serum sB7-H4, an immunological checkpoint molecule, and placental proteins (Flt-1, Eng, B7-H4, iNOS, TNF-α) in TPE-treated early-onset preeclampsia patients (N = 12, 23 + 2-28 + 5 weeks), conventionally treated counterparts (N = 12, 23 + 5-30 weeks), and gestational age-matched controls (N = 8, 22 + 4-31 + 6 weeks). Immunoblotting, ELISA, and co-immunohistochemistry were used for biomarker analysis, including placental inflammation factors (iNOS, TNF-α). The results showed that TPE extended pregnancy by a median of 6.5 days in this cohort of early-onset preeclampsia. Serum sB7-H4, sFlt-1, and sEndoglin levels decreased, along with reduced expression of their membrane-bound proteins in placental tissue upon TPE treatment. Moreover, TPE-treated patients displayed reduced placental inflammation compared to preeclampsia patients receiving standard-of-care treatment. In conclusion, TPE may improve pregnancy outcomes in early-onset preeclampsia by lowering circulating levels of sB7-H4, sFlt-1, and sEndoglin, as well as reducing placental inflammation. This translational approach holds promise for enhancing placental function and extending gestation in high-risk pregnancies including very preterm PE or HELLP cases.

Coagulation factor XI (FXI) has increasingly been shown to play an integral role in several physiologic and pathological processes. FXI is among several zymogens within the blood coagulation cascade that are activated by proteolytic cleavage, with FXI converting to the active serine protease form (FXIa). The evolutionary origins of FXI trace back to duplication of the gene that transcribes plasma prekallikrein, a key factor in the plasma kallikrein-kinin system, before further genetic divergence led to FXI playing a unique role in blood coagulation. While FXIa is canonically known for activating the intrinsic pathway of coagulation by catalyzing the conversion of FIX into FIXa, it is promiscuous in nature and has been shown to contribute to thrombin generation independent of FIX. In addition to its role in the intrinsic pathway of coagulation, FXI also interacts with platelets, endothelial cells, and mediates the inflammatory response through activation of FXII and cleavage of high-molecular-weight kininogen to generate bradykinin. In this manuscript, we critically review the current body of knowledge surrounding how FXI navigates the interplay of hemostasis, inflammatory processes, and the immune response and highlight future avenues for research. As FXI continues to be clinically explored as a druggable therapeutic target, understanding how this coagulation factor fits into physiological and disease mechanisms becomes increasingly important.

Manganese (Mn) is an essential trace element involved in various physiological processes, but excessive exposure may lead to toxicity. The vascular endothelium, a monolayer of endothelial cells within blood vessels, is a primary target of Mn toxicity. This review provides a comprehensive overview of the impact of Mn on vascular endothelium, focusing on both peripheral and brain endothelial cells. In vitro studies have demonstrated that high concentrations of Mn can induce endothelial cell cytotoxicity, increase permeability, and disrupt cell-cell junctions through mechanisms involving oxidative stress, mitochondrial damage, and activation of signaling pathways, such as Smad2/3-Snail. Conversely, low concentrations of Mn may protect endothelial cells from the deleterious effects of high glucose and advanced glycation end-products. In the central nervous system, Mn can cross the blood-brain barrier (BBB) and accumulate in the brain parenchyma, leading to neurotoxicity. Several transport mechanisms, including ZIP8, ZIP14, and SPCA1, have been identified for Mn uptake by brain endothelial cells. Mn exposure can impair BBB integrity by disrupting tight junctions and increasing permeability. In vivo studies have corroborated these findings, highlighting the importance of endothelial barriers in mediating Mn toxicity in the brain and kidneys. Maintaining optimal Mn homeostasis is crucial for preserving endothelial function, and further research is needed to develop targeted therapeutic strategies to prevent or mitigate the adverse effects of Mn overexposure.

The dysfunction of blood-vessel-lining endothelial cells is a major cause of mortality. Although endothelial cells, being present in all organs as a single-cell layer, are often conceived as a rather inert cell population, the vascular endothelium as a whole should be considered a highly dynamic and interactive systemically disseminated organ. We present here a holistic view of the field of vascular research and review the diverse functions of blood-vessel-lining endothelial cells during the life cycle of the vasculature, namely responsive and relaying functions of the vascular endothelium and the responsive roles as instructive gatekeepers of organ function. Emerging translational perspectives in regenerative medicine, preventive medicine, and aging research are developed. Collectively, this review is aimed at promoting disciplinary coherence in the field of angioscience for a broader appreciation of the importance of the vasculature for organ function, systemic health, and healthy aging.

Ischemic and/or infarction events of the alimentary canal are uncommon but potentially disastrous injuries of the digestive system that often portend a poor prognosis. Alimentary ischemia occurs when the vascular supply to one of the component conduit organs is disrupted or blocked, resulting in decreased tissue perfusion, subsequent necrosis, perforation, and even death if proper perfusion is not restored. We report a case here of a 67-year-old female who originally presented to the emergency department (ED) with nausea, vomiting, diarrhea, and progressively worsening abdominal pain. Conservative therapies that were initially employed failed to provide lasting symptom relief, and the patient was admitted for a more in-depth diagnostic workup and closer monitoring. During subsequent days of her resulting hospital stay, the patient had a positive result for Salmonella spp. on a stool PCR assay, an increasing leukocytosis, and the presence of several other worrisome laboratory abnormalities. Despite appropriate antibiotics and aggressive fluid resuscitation efforts, the patient's abdominal pain and laboratory profile continued to progressively worsen. At one point, the patient's condition perilously worsened, necessitating an emergent exploratory laparotomy. During the course of this surgery and subsequent surgeries, the patient was found to have multiple areas of infarction present including at her esophagus, stomach, duodenum, proximal jejunum, and right colon. Additionally, evidence of a metastatic neuroendocrine tumor of gastrointestinal (GI) origin was also incidentally found. Several subsequent surgical operations were required to repair the extensive tissue damage that the patient had sustained, and the patient's resulting hospital stay was complicated repeatedly by several different secondary infections and surgical complications. Attempts to determine the underlying cause for the ischemic events this patient experienced failed to yield definitive results, and no evidence for any arterial insufficiency or emboli was ever discovered. Despite this, a review of the histopathologic and laboratory findings from the tissue resected from the patient did find information to suggest that a relatively localized but severe venous thrombotic process likely occurred in the patient's alimentary vasculature that directly led to her presentation. Venous thrombosis of the mesenteric vessels and in the other vascular planes of the alimentary canal is often insidious in its presentation and poses a unique diagnostic challenge to clinicians. This case is significant because it illustrates the diagnostic complexity and difficulty imposed by mesenteric ischemia, especially cases resulting from mesenteric venous thrombosis (MVT) due to their often more indolent and atypical presentation. In short, a high level of clinical suspicion and familiarity with this ailment and its risk factors should be maintained because, in the absence of timely intervention, significant morbidity and/or mortality are likely to result.

This review article discussed the use of bridging therapy with low-molecular-weight heparin (LMWH) in patients who undergo noncardiac surgery (NCS) after percutaneous coronary intervention (PCI).

Patients who undergo PCI are at an increased risk of thrombotic events due to their underlying cardiovascular disease. However, many of these patients may require NCS at some point in their lives, which poses a significant challenge for clinicians as they balance the risk of thrombotic events against the risk of bleeding associated with antithrombotic therapy.

This review evaluates the current evidence on the use of bridging therapy with LMWH in patients undergoing NCS after PCI, focusing on outcomes related to the efficacy and safety of antithrombotic therapy. The article also discusses the limitations of the current evidence and highlights areas where further research is needed to optimize the management of antithrombotic therapy in this patient population.

The goal of this review was to provide clinicians with a comprehensive summary of the available evidence to guide clinical decision-making and improve patient outcomes.