Epidithio-diketopiperazine (ETP) compound is the family of natural fungal metabolites that are known to exert diverse biological effects, such as immunosuppression and anti-cancer activity, in higher animals. However, an enzyme-like catalytic activity or function of the ETP derivatives has not been reported. Here, we report the generation of novel thiol peroxidase mimetics that possess peroxide-reducing activity through strategic derivatization of the core ETP ring structure. The ETP derivatives with small side chains are the bona fide 2-Cys peroxiredoxin (PRX) mimetics that catalyze the H2O2-reducing reaction specifically coupled to the thioredoxin/thioredoxin reductase system. In contrast, the ETP derivatives with linear chains or a heterocyclic group show H2O2-reducing activity in coupling with both thioredoxin and glutathione systems. Moreover, the ETP derivatives with bulky heterocyclic groups almost lose catalytic activity. The 2-Cys PRX mimetics regulate intracellular H2O2 levels, thereby restoring the receptor Tyr kinase signaling and cellular functions disrupted by the absence of 2-Cys PRX in vascular cells. In a rodent model, the 2-Cys PRX mimetics reverse vascular occlusion in the injured carotid arteries by inhibiting smooth muscle hyperplasia and promoting reendothelialization. Thus, this study reveals a novel chemical platform for complementing defective 2-Cys PRX enzymes in biological systems.

Low-density lipoprotein (LDL) is the primary natural carrier of lipids in the bloodstream and plays a central role in the development of atherosclerosis. By leveraging LDL's natural tendency to accumulate at sites of plaque formation, LDL can be employed as a carrier to selectively deliver the imaging probes to efficiently detect atherosclerotic plaques. In our previous studies, we reported several LDL-based magnetic resonance imaging contrast agents (MRI-CAs) formed by modifying natural LDL (nLDL) or developing LDL-mimetic (synthetic LDL, sLDL) from lipid nanoparticles (LNPs) utilizing chemical reactions on the nanoparticle surface, including preliminary MRI tests. In this study, we report the in vivo biological functionality of these LDLs (both nLDL and sLDL)-based Gd(III)-based contrast agents (GBCAs) by conducting detailed in vivo studies on two types of atherosclerosis murine models, namely, apoE -/- and LDLr -/- . We provide more comprehensive MRI data accompanied by ex vivo results, including microscopic analysis of aorta segments for LDL accumulation and whole-body cryoVIZ analysis for biodistribution of the probe. We also tested in vitro cellular internalization of sLDL on two cell lines (RAW 264.7 and THP-1), which are derived from macrophages and monocytes, respectively, in order to observe sLDL uptake by macrophages, which are often present at the vulnerable types of atherosclerotic plaques. In conclusion, our current study demonstrates that modified LDLs-both nLDL and sLDL-facilitate MRI detection of atheroplaques by efficient uptake by macrophages. Taken together with the high loading capacity of Gd(III)-chelate molecules on LDL, especially sLDL, the LDL-based MRI contrast agents reported here hold significant potential for the early detection of atherosclerosis, including vulnerable ones, and should be useful for preventive diagnosis strategies.

Cardiovascular disease (CVD) caused by atherosclerosis (AS) remains the leading cause of mortality in developed countries. Understanding cellular heterogeneity within the inflammatory microenvironment is crucial for advancing disease management strategies. This study investigates the regulatory functions of distinct cell populations in AS pathogenesis, focusing on the interaction between vascular smooth muscle cell (VSMC)-derived ITLN1+ foam cells and SPP1+ FABP5+ macrophages.

We employed single-cell RNA sequencing to characterize cell populations within AS plaques. Correlation analyses and the CellChat package were utilized to elucidate intercellular communication networks among various cell types. The functional roles of key subsets of macrophages and VSMCs were assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Pseudotime trajectory analysis was conducted to explore the dynamics of VSMC differentiation. Additionally, spatial transcriptomics analysis was used to demonstrate the physical interactions between different cell subpopulations.

We identified significant infiltration of macrophage clusters in AS, with SPP1+ FABP5+ macrophages being highly enriched in AS plaques. These macrophages were associated with lipid transport, storage, and cell migration pathways. A distinct subset of ITLN1+ foam cells derived from VSMCs exhibited robust expression of foam cell markers and lipid metabolism-related genes. Pseudotime trajectory analysis indicated that ITLN1+ foam cells represent a terminal stage of VSMC differentiation, characterized by elevated expression of genes linked to lipid synthesis and AS progression. Spatial transcriptomics and CellChat analysis revealed a significant interaction between ITLN1+ foam cells and SPP1+ FABP5+ macrophages, mediated by the MIF-(CD74 + CD44) and SPP1-CD44 ligand-receptor axes.

Our findings underscore the critical crosstalk between ITLN1+ foam cells and SPP1+ macrophages in promoting lipid accumulation and AS progression. Targeting this cell-cell interaction may offer new therapeutic avenues for managing atherosclerosis. Further validation of these mechanisms is necessary to develop effective immunotherapeutic strategies against AS.

This review discusses the increasing global trend towards an aging population, which has resulted in a growing number of surgeries being performed on elderly patients, particularly those living with cancer. The focus was on the implications of abdominal aortic calcification (AAC), an indicator of systemic atherosclerosis, in these patients. This comprehensive review provided evidence detailing the complex processes of atherosclerosis and vascular calcification and various approaches to assess this condition. The prevalence of AAC is related to multiple factors, including cardiovascular disease, inflammation, frailty in various types of gastroenterological surgery. Additionally, notable links were found between AAC, postoperative complications, and patient survival following gastroenterological surgery. This study highlights how AAC could negatively impact the health status of elderly patients and undermine treatment efficacy, stressing the need for more research in this domain to improve patient outcomes.

Endothelial shear stress is a tangential stress derived from the friction of the flowing blood on the endothelial surface of the arterial wall and is expressed in units of force/unit area (dyne/cm2). Branches and bends of arteries are exposed to complex blood flow patterns that generate low or oscillatory endothelial shear stress, which impairs glycocalyx integrity, cytoskeleton arrangement and endothelial junctions (adherens junctions, tight junctions, gap junctions), thus increasing endothelial permeability. The lipoproteins and inflammatory cells penetrating intima due to the increased endothelial permeability characterizes the pathological changes in early stage of atherosclerosis. Endothelial cells are critical sensors of shear stress, however, the mechanisms by which the complex shear stress regulate endothelial permeability in atherosclerosis remain unclear. In this review, we focus on the molecular mechanisms of the endothelial permeability induced by low or oscillatory shear stress, which will shed a novel sight in early stage of atherosclerosis.

Visualizing (micro)vascular structures remains challenging for researchers and clinicians due to limitations in traditional radiological imaging methods. Exploring the role of vascular development in craniofacial malformations in experimental settings can enhance understanding of these processes, with the effectiveness of high-resolution imaging techniques being crucial for successful research in this field. Micro-CT imaging offers 3D microstructural insights, but requires contrast-enhancing staining agents (CESAs) for visualizing (micro)-vascular tissues, known as contrast-enhanced micro-CT (CECT). As effective contrast agents are crucial for optimal visualization, this review focuses on comparative studies investigating such agents for micro-vascular tissue imaging using micro-CT. Furthermore, we demonstrate the utilization of B-Lugol solution as a promising contrast agent for acquiring high-quality micro-CT images of (micro)vascular structures in human embryonic samples.

This scoping review followed Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols. PubMed database provided relevant articles, screened initially by title and abstract. Inclusion and exclusion criteria defined outcomes of interest.

From an initial search, 273 records were identified, narrowed down to 9 articles after applying our criteria. Additionally, two articles were added through citation searching. This, a total of 11 articles were incorporated in this study.

This micro-CT contrast agent review underscores the need for tailored choices based on research goals. Both Barium sulfate and Iodine-based agents showing excellent results, providing high resolution (micro) vascular content, especially in ex-vivo specimens. However, careful consideration of protocols and tissue characteristics remains imperative for optimizing the effectiveness of micro-CT imaging for the study of cranio-facial vascular development.

Atherosclerosis (AS) is a dominant pathological basis of cardiovascular disease. Circular RNAs (circRNAs) have been proposed to have crucial functions in regulating pathological progressions of AS. Hence, the aim of this study was to investigate the potential function of circ_0090231 in AS progression. Oxidized low densitylipoprotein (ox-LDL)-challenged vascular smooth muscle cells (VSMCs) were used for in vitro functional analysis. Levels of genes and proteins were measured by qRT-PCR and Western blot. The proliferation, migration and invasion were assessed using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and transwell assays. The interaction between miR-942-5p and circ_0090231 or PPM1B (Protein Phosphatase, Mg2+/Mn2+ Dependent 1B) was evaluated by dual-luciferase reporter and pull-down assays. Circ_0090231 is a stable circRNA, and was increased in the serum of AS patients and ox-LDL-challenged VSMCs. Functionally, silencing of circ_0090231 could reverse ox-LDL-induced proliferation, migration and invasion in VSMCs. Mechanistically, circ_0090231 directly targeted miR-942-5p, and PPM1B was a target of miR-942-5p. Besides, circ_0090231 sequestered miR-942-5p to release PPM1B expression, suggesting the circ_0090231/miR-942-5p/PPM1B axis. Further rescue experiments showed that miR-942-5p inhibition or ectopic overexpression of PPM1B dramatically attenuated the suppressing influences of circ_0090231 knockdown on VSMC proliferative, migratory and invasive abilities under ox-LDL treatment. Silencing of circ_0090231 could reverse ox-LDL-induced proliferation, migration and invasion in VSMCs via miR-942-5p/PPM1B axis, providing a theoretical basis for elucidating the mechanism of AS process.

Atherosclerosis (AS) is a significant global health concern due to its high morbidity and mortality rates. Extensive efforts have been made to replicate the cardiovascular system and explore the pathogenesis, diagnosis, and treatment of AS. Microfluidics has emerged as a valuable technology for modeling the cardiovascular system and studying AS. Here a brief review of the advances of microfluidic-based cardiovascular systems for AS research is presented. The critical pathogenetic mechanisms of AS investigated by microfluidic-based cardiovascular systems are categorized and reviewed, with a detailed summary of accurate diagnostic methods for detecting biomarkers using microfluidics represented. Furthermore, the review covers the evaluation and screening of AS drugs assisted by microfluidic systems, along with the fabrication of novel drug delivery carriers. Finally, the challenges and future prospects for advancing microfluidic-based cardiovascular systems in AS research are discussed and proposed, particularly regarding new opportunities in multi-disciplinary fundamental research and therapeutic applications for a broader range of disease treatments.

To reduce the risk of atherosclerotic disease, it is necessary to not only diagnose the presence of atherosclerotic plaques but also assess the vulnerability risk of plaques. Accurate detection of the reactive oxygen species (ROS) level at plaque sites represents a reliable way to assess the plaque vulnerability. Herein, through a simple one-pot reaction, two near-infrared (NIR) fluorescent dyes, one is ROS responsive and the other is inert to ROS, are coassembled in an amphiphilic amino acid-assembled nanoparticle. In the prepared NIR fluorescent amino acid nanoparticle (named FANP), the fluorescent properties and ROS-responsive behaviors of the two fluorescent dyes are well maintained. Surface camouflage through red blood cell membrane (RBCM) encapsulation endows the finally obtained FANP@RBCM nanoprobe with not only further reduced cytotoxicity and improved biocompatibility but also increased immune escape capability, prolonged blood circulation time, and thus enhanced accumulation at atherosclerotic plaque sites. In vitro and in vivo experiments demonstrate that FANP@RBCM not only works well in probing the occurrence of atherosclerotic plaques but also enables plaque vulnerability assessment through the accurate detection of the ROS level at plaque sites in a reliable ratiometric mode, thereby holding great promise as a versatile tool for the diagnosis and risk assessment of atherosclerotic disease.

Atherosclerosis (AS) stands as the primary contributor to cardiovascular disease, a pervasive global health concern. Extensive research has underscored the pivotal role of circular RNAs (circRNAs) in cardiovascular disease development. However, the specific functions of numerous circRNAs in AS remain poorly understood.

Quantitative real-time PCR analysis revealed a significant upregulation of circ_0104652 in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs). Loss-of-function experiments were subsequently employed to assess the impact of circ_0104652 on ox-LDL-induced VSMCs.

Silencing circ_0104652 was found to impede the proliferation and migration while promoting the apoptosis of ox-LDL-stimulated VSMCs. Mechanistic assays unveiled that circ_0104652 stabilized ADAM metallopeptidase with thrombospondin type 1 motif 7 (ADAMTS7) and high mobility group box 1 (HMGB1) by recruiting eukaryotic translation initiation factor 4A3 (EIF4A3) protein. Rescue assays further confirmed that circ_0104652 exerted its influence on ox-LDL-induced VSMC proliferation through modulation of ADAMTS7 and HMGB1.

This study elucidates the role of the circ_0104652/EIF4A3/ADAMTS7/HMGB1 axis in ox-LDL-stimulated VSMCs, providing valuable insights into the intricate mechanisms involved.

Techniques for imaging haemodynamics use ionizing radiation or contrast agents or are limited by imaging depth (within approximately 1 mm), complex and expensive data-acquisition systems, or low imaging speeds, system complexity or cost. Here we show that ultrafast volumetric photoacoustic imaging of haemodynamics in the human body at up to 1 kHz can be achieved using a single laser pulse and a single element functioning as 6,400 virtual detectors. The technique, which does not require recalibration for different objects or during long-term operation, enables the longitudinal volumetric imaging of haemodynamics in vasculature a few millimetres below the skin's surface. We demonstrate this technique in vessels in the feet of healthy human volunteers by capturing haemodynamic changes in response to vascular occlusion. Single-shot volumetric photoacoustic imaging using a single-element detector may facilitate the early detection and monitoring of peripheral vascular diseases and may be advantageous for use in biometrics and point-of-care testing.

Ketogenic diets (KDs) are very high-fat low-carbohydrate diets that promote nutritional ketosis and are widely used for weight loss, although concerns about potential adverse cardiovascular effects remain. We investigated a very high-fat KD's vascular impact and plasma metabolic signature compared to a non-ketogenic high-fat diet (HFD). Apolipoprotein E deficient (ApoE -/-) mice were fed a KD (%kcal:81:1:18, fat/carbohydrate/protein), a non-ketogenic high-fat diet with half of the fat content (HFD) (%kcal:40:42:18, fat/carbohydrate/protein) for 12 weeks. Plasma samples were used to quantify the major ketone body beta-hydroxybutyrate (BHB) and several pro-inflammatory cytokines (IL-6, MCP-1, MIP-1alpha, and TNF alpha), and to targeted metabolomic profiling by mass spectrometry. In addition, aortic atherosclerotic lesions were quantified ex-vivo by magnetic resonance imaging (MRI) on a 14-tesla system. KD was atherogenic when compared to the control diet, but KD mice, when compared to the HFD group (1) had markedly higher levels of BHB and lower levels of cytokines, confirming the presence of ketosis that alleviated the well-established fat-induced systemic inflammation; (2) displayed significant changes in the plasma metabolome that included a decrease in lipophilic metabolites and an increase in hydrophilic metabolites; (3) had significantly lower levels of several atherogenic lipid metabolites, including phosphatidylcholines, cholesterol esters, sphingomyelins, and ceramides; and (4) presented significantly lower aortic plaque burden. KD was atherogenic and was associated with specific metabolic changes but alleviated the fat-induced inflammation and lessened the progression of atherosclerosis when compared to the HFD.

Atherosclerosis(AS) poses a pressing challenge in contemporary medicine. Formononetin (FMN) plays a crucial role in its prevention and treatment. However, the detailed impact of FMN on the stability of atherosclerotic plaques and its underlying mechanisms remain to be elucidated.

An intervention consisting of FMN was given along with a high-fat food regimen in the ApoE-/- mouse model. The investigation included the evaluation of the degree of atherosclerotic lesion, the main components of the plaque, lipid profiles, particular markers indicating M1/M2 macrophage phenotypes, the quantities of factors related to inflammation, the infiltration of macrophages, and the identification of markers linked to the α7nAChR/JAK2/STAT3 axis effect molecules.

The evaluation of aortic morphology in ApoE-/-mice revealed that FMN significantly improved the plaque area, fibrous cap protrusion, lipid deposition, and structural alterations on the aortic surface, among other markers of atherosclerosis,and there is concentration dependence. Furthermore, the lipid content of mouse serum was assessed, and the results showed that the low-, medium-, and high-dosage FMN groups had significantly lower levels of LDL-C, ox-LDL, TC, and TG. The results of immunohistochemical staining indicated that the low-, medium-, and high-dose FMN therapy groups had enhanced CD206 expression and decreased expression of CD68 and iNOS. According to RT-qPCR data, FMN intervention has the potential to suppress the expression of iNOS, COX-2, miR-155-5p, IL-6, and IL-1β mRNA, while promoting the expression of IL-10, SHIP1, and Arg-1 mRNA levels. However, the degree of inhibition varied among dosage groups. Western blot investigation of JAK/STAT signaling pathway proteins and cholinergic α7nAChR protein showed that p-JAK2 and p-STAT3 protein expression was suppressed at all dosages, whereas α7nAChR protein expression was enhanced.

According to the aforementioned findings, FMN can reduce inflammation and atherosclerosis by influencing macrophage polarization, blocking the JAK/STAT signaling pathway, and increasing α7nAChR expression.

This study aimed at modelling the underlying predictor of ASCVD through the Bayesian network (BN). Data for the AZAR Cohort Study, which evaluated 500 healthcare providers in Iran, was collected through examinations, and blood samples. Two BNs were used to explore a suitable causal model for analysing the underlying predictor of ASCVD; Bayesian search through an algorithmic approach and knowledge-based BNs. Results showed significant differences in ASCVD risk factors across background variables' levels. The diagnostic indices showed better performance for the knowledge-based BN (Area under ROC curve (AUC) = 0.78, Accuracy = 76.6, Sensitivity = 62.5, Negative predictive value (NPV) = 96.0, Negative Likelihood Ratio (LR-) = 0.48) compared to Bayesian search (AUC = 0.76, Accuracy = 72.4, Sensitivity = 17.5, NPV = 93.2, LR- = 0.83). In addition, we decided on knowledge-based BN because of the interpretability of the relationships. Based on this BN, being male (conditional probability = 63.7), age over 45 (36.3), overweight (51.5), Mets (23.8), diabetes (8.3), smoking (10.6), hypertension (12.1), high T-C (28.5), high LDL-C (23.9), FBS (12.1), and TG (25.9) levels were associated with higher ASCVD risk. Low and normal HDL-C levels also had higher ASCVD risk (35.3 and 37.4), while high HDL-C levels had lower risk (27.3). In conclusion, BN demonstrated that ASCVD was significantly associated with certain risk factors including being older and overweight male, having a history of Mets, diabetes, hypertension, having high levels of T-C, LDL-C, FBS, and TG, but Low and normal HDL-C and being a smoker. The study may provide valuable insights for developing effective prevention strategies for ASCVD in Iran.

Simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) is a novel hybrid imaging method integrating the advances of morphological tissue characterization of MRI with the pathophysiological insights of PET applications.

This study evaluated the use of simultaneous 18-FDG PET/MR imaging for characterizing atherosclerotic lesions in lower extremity arterial disease (LEAD).

Eight patients with symptomatic stenoses of the superficial femoral artery (SFA) under simultaneous acquisition of 18-FDG PET and contrast-enhanced MRI using an integrated whole-body PET/MRI scanner. Invasive plaque characterization of the SFA was performed by intravascular imaging using optical coherence tomography. Histological analysis of plaque specimens was performed after directional atherectomy.

MRI showed contrast enhancement at the site of arterial stenosis, as assessed on T2-w and T1-w images, compared to a control area of the contralateral SFA (0.38 ± 0.15 cm vs. 0.23 ± 0.11 cm; 1.77 ± 0.19 vs. 1.57 ± 0.15; p-value <0.05). On PET imaging, uptake of 18F-FDG (target-to-background ratio TBR > 1) at the level of symptomatic stenosis was observed in all but one patient. Contrast medium-induced MR signal enhancement was detected in all plaques, whereas FDG uptake in PET imaging was increased in lesions with active fibroatheroma and reduced in fibrocalcified lesions.

In this multimodal imaging study, we report the feasibility and challenges of simultaneous PET/MR imaging of LEAD, which might offer new perspectives for risk estimation.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide and its incidence is rising due to an aging population. The development and progression of CVD is directly linked to adverse vascular hemodynamics and biomechanics, whose in-vivo measurement remains challenging but can be simulated numerically and experimentally. The ability to evaluate these parameters in patient-specific CVD cases is crucial to better predict future disease progression, risk of adverse events, and treatment efficacy. While significant progress has been made toward patient-specific hemodynamic simulations, blood vessels are often assumed to be rigid, which does not consider the compliant mechanical properties of vessels whose malfunction is implicated in disease. In an effort to simulate the biomechanics of flexible vessels, fluid-structure interaction (FSI) simulations have emerged as promising tools for the characterization of hemodynamics within patient-specific cardiovascular anatomies. Since FSI simulations combine the blood's fluid domain with the arterial structural domain, they pose novel challenges for their experimental validation. This paper reviews the scientific work related to FSI simulations for patient-specific arterial geometries and the current standard of FSI model validation including the use of compliant arterial phantoms, which offer novel potential for the experimental validation of FSI results.

Room-temperature phosphorescent (RTP) materials have great potential for in vivo imaging because they can circumvent the autofluorescence of biological tissues. In this study, a class of organic-doped long-wavelength (≈600 nm) RTP materials with benzo[c][1,2,5] thiadiazole as a guest was constructed. Both host and guest molecules have simple structures and can be directly purchased commercially at a low cost. Owing to the long phosphorescence wavelength of the doping system, it exhibited good tissue penetration (10 mm). Notably, these RTP nanoparticles were successfully used to image atherosclerotic plaques, with a signal-to-background ratio (SBR) of 44.52. This study provides a new approach for constructing inexpensive red organic phosphorescent materials and a new method for imaging cardiovascular diseases using these materials.

Atherosclerosis is a lipoprotein-driven disease, and there is no effective therapy to reverse atherosclerosis or existing plaques. Therefore, it is urgently necessary to create a noninvasive and reliable approach for early atherosclerosis detection to prevent initial plaque formation. Atherosclerosis is intimately associated with inflammation, which is accompanied by an excess of reactive oxygen species (ROS), leading to cells requiring more glutathione (GSH) to resist severe oxidative stress. Therefore, the GSH-hydrolyzed protein γ-glutamyl transpeptidase (GGT) and the ROS-hypobromous acid (HBrO) are potential biomarkers for predicting atherogenesis. Hence, to avoid false-positive diagnoses caused by a single biomarker, we constructed an ingenious sequence-activated double-locked TP fluorescent probe, C-HBrO-GGT, in which two sequential triggers of GGT and HBrO are meticulously designed to ensure that the probe fluoresces in response to HBrO only after GGT hydrolyzes the probe. By utilization of C-HBrO-GGT, the voltage-gated chloride channel (CLC-1)-HBrO-catalase (CAT)-GGT signaling pathway was confirmed in cellular level. Notably, the forthcoming atherosclerotic plaques were successfully predicted before the plaques could be observed via the naked eye or classical immunofluorescent staining. Collectively, this research proposed a powerful tool to indicate the precise position of mature plaques and provide early warning of atherosclerotic plaques.

Ruling out obstructive coronary artery disease (CAD) using coronary computed tomography angiography (CCTA) is time-consuming and challenging. This study developed a deep learning (DL) model to assist in detecting obstructive CAD on CCTA to streamline workflows.

In total, 2929 DICOM files and 7945 labels were extracted from curved planar reformatted CCTA images. A modified Inception V3 model was adopted. To validate the artificial intelligence (AI) model, two cardiologists labelled and adjudicated the classification of coronary stenosis on CCTA. The model was trained to differentiate the coronary artery into binary stenosis classifications <50% and ≥50% stenosis. Using the quantitative coronary angiography (QCA) consensus results as a reference standard, the performance of the AI model and CCTA radiology readers was compared by calculating Cohen's kappa coefficients at patient and vessel levels. The net reclassification index was used to evaluate the net benefit of the DL model.

The diagnostic accuracy of the AI model was 92.3% and 88.4% at the patient and vessel levels, respectively. Compared with CCTA radiology readers, the AI model had a better agreement for binary stenosis classification at both patient and vessel levels (Cohen kappa coefficient: .79 vs. .39 and .77 vs. .40, p < .0001). The AI model also exhibited significantly improved model discrimination and reclassification (Net reclassification index = .350; Z = 4.194; p < .001).

The developed AI model identified obstructive CAD, and the model results correlated well with QCA results. Incorporating the model into the reporting system of CCTA may improve workflows.

Imaging technologies that provide detailed information on intricate shapes and states of an object play critical roles in nanoscale dynamics, bio-organ and cell studies, medical diagnostics, and underwater detection. However, ultrasonic imaging of an object hidden by a nearly impenetrable metal barrier remains intractable. Here, we present the experimental results of ultrasonic imaging of an object in water behind a metal barrier of a high impedance mismatch. In comparison to direct ultrasonic images, our method yields sufficient object information on the shapes and locations with minimal errors. While our imaging principle is based on the Fabry-Perot (FP) resonance, our strategy for reducing attenuation in our experiments focuses on customising the resonance at any desired frequency. To tailor the resonance frequency, we placed an elaborately engineered panel of a specific material and thickness, called the FP resonance-tailoring panel (RTP), and installed the panel in front of a barrier at a controlled distance. Since our RTP-based imaging technique is readily compatible with conventional ultrasound devices, it can realise underwater barrier-through imaging and communication and enhance skull-through ultrasonic brain imaging.

The aim of this study was to investigate the potential value of intracranial carotid artery calcification (ICAC) in therapeutic efficacy and functional outcomes in patients with anterior circulation acute ischemic stroke (AIS) undergoing intravenous thrombolysis.

A total of 207 patients with anterior circulation AIS who underwent intravenous thrombolysis were enrolled in this retrospective study. We divided them into three groups according to thin-slice head noncontrast computed tomography as follows: no ICAC, medial ICAC, and intimal ICAC. The differences in risk factors of different ICAC subtypes were compared, and the effect of ICAC subtype on hemorrhage transformation (HT) after intravenous thrombolysis was also evaluated. Functional outcomes were assessed at 90 days using the modified Rankin Scale.

Compared to the no and intimal ICAC, patients with the medial ICAC were older and more likely to have diabetes mellitus, hyperlipidemia, previous stroke, and atrial fibrillation. Moreover, the medial ICAC group had a high baseline National Institute of Health Stroke Scale (NIHSS) score and a high incidence of HT. Multivariate logistic regression analysis showed that baseline NIHSS score (odds ratio [OR]: 1.121, 95% confidence interval [CI]: 1.027-1.224) was independently associated with HT. Medial ICAC (OR: 7.418, 95% CI: 1.190-46.231) and baseline NIHSS score (OR: 1.141, 95% CI: 1.042-1.250) were independent risk factors of poor functional outcome at 90 days.

Medial ICAC could be a new imaging biomarker for predicting functional outcomes in patients with anterior circulation AIS undergoing intravenous thrombolysis. Medial ICAC and baseline NIHSS score were independently associated with poor prognosis at 90 days.

Oxidative stress is integral in the development of atherosclerosis, but knowledge of how oxidative stress affects atherosclerosis remains insufficient. Here, we design a multiplexed diagnostic tool that includes two functions (photoacoustic imaging and urinalysis), for assessing intraplaque and urinary malondialdehyde (MDA), a well-recognized end-product of oxidative stress. Molecular design is conducted to develop the first near-infrared MDA-responsive molecule (MRM). Acid-unlocked ratiometric photoacoustic nanoprobe is designed to report intraplaque MDA, enabling it to reflect plaque burden. Furthermore, MRM is tailored for urinary MDA detection with excellent specificity in a blind study. Moreover, we found a significant difference in urinary MDA between healthy adults and atherosclerotic patients (more than 600 participants). Combining these two functions, such a multiplexed diagnostic tool can dynamically report intraplaque and systemic oxidative stress levels during atherosclerosis progression, pneumonia infection, and drug treatment in atherosclerotic mice, which is promising for the auxiliary diagnosis of atherosclerosis.

Vascular compliance is considered both a cause and a consequence of cardiovascular disease and a significant factor in the mid- and long-term patency of vascular grafts. However, the biomechanical effects of localised changes in compliance cannot be satisfactorily studied with the available medical imaging technologies or surgical simulation materials. To address this unmet need, we developed a coupled silico-vitro platform which allows for the validation of numerical fluid-structure interaction results as a numerical model and physical prototype. This numerical one-way and two-way fluid-structure interaction study is based on a three-dimensional computer model of an idealised femoral artery which is validated against patient measurements derived from the literature. The numerical results are then compared with experimental values collected from compliant arterial phantoms via direct pressurisation and ring tensile testing. Phantoms within a compliance range of 1.4-68.0%/100 mmHg were fabricated via additive manufacturing and silicone casting, then mechanically characterised via ring tensile testing and optical analysis under direct pressurisation with moderately statistically significant differences in measured compliance ranging between 10 and 20% for the two methods. One-way fluid-structure interaction coupling underestimated arterial wall compliance by up to 14.7% compared with two-way coupled models. Overall, Solaris™ (Smooth-On) matched the compliance range of the numerical and in vivo patient models most closely out of the tested silicone materials. Our approach is promising for vascular applications where mechanical compliance is especially important, such as the study of diseases which commonly affect arterial wall stiffness, such as atherosclerosis, and the model-based design, surgical training, and optimisation of vascular prostheses.

Plaque rupture is a critical concern due to its potential for severe outcomes such as cerebral infarction and myocardial infarction, underscoring the urgency of noninvasive early diagnosis. Magnetic resonance imaging (MRI) has gained prominence in plaque imaging, leveraging its noninvasiveness, high spatial resolution, and lack of ionizing radiation. Ultrasmall iron oxides, when modified with polyethylene glycol, exhibit prolonged blood circulation and passive targeting toward plaque sites, rendering them conducive for MRI. In this study, we synthesized ultrasmall iron oxide nanoparticles of approximately 3 nm via high-temperature thermal decomposition. Subsequent surface modification facilitated the creation of a dual-modality magnetic resonance/fluorescence probe. Upon intravenous administration of the probes, MRI assessment of atherosclerotic plaques and diagnostic evaluation were conducted. The application of Flash-3D sequence imaging revealed vascular constriction at lesion sites, accompanied by a gradual signal amplification postprobe injection. T1-weighted imaging of the carotid artery unveiled a progressive signal ratio increase between plaques and controls within 72 h post-administration. Fluorescence imaging of isolated carotid arteries exhibited incremental lesion-to-control signal ratios. Additionally, T1 imaging of the aorta demonstrated an evolving signal enhancement over 48 h. Therefore, the ultrasmall iron oxide nanoparticles hold immense promise for early and noninvasive diagnosis of plaques, providing an avenue for dynamic evaluation over an extended time frame.

Various bioactive substances are simultaneously involved in physiological processes, and research on the synergistic effect of them can promote the study of pathological mechanisms. To achieve this purpose, several small-molecule double-locked logic gate fluorescence probes have been developed recently. They overcome many shortcomings of the traditional "single-signal" fluorescent probes, with fluorescence that can be activated by two analytes of interest order-independently or order-dependently with one output. In this review, we summarize recently published small-molecule double-locked logic gate probes for the optical detection of two bioactive substances in living systems. We envision that this review will attract significant attention from researchers to exploit more powerful functional double-locked logic gate probes.

Second near infrared (NIR-II, 1000-1700 nm) fluorescence lifetime imaging is a powerful tool for biosensing, anti-counterfeiting, and multiplex imaging. However, the low photoluminescence quantum yield (PLQY) of fluorescence probes in NIR-II region limits its data collecting efficiency and accuracy, especially in multiplex molecular imaging in vivo. To solve this problem, lanthanide-doped nanoparticles (NPs) β-NaErF4 : 2%Ce@NaYbF4 @NaYF4 with high PLQY and tunable PL lifetime through multi-ion doping and core-shell structural design, are presented. The obtained internal PLQY can reach up to 50.1% in cyclohexane and 9.2% in water under excitation at 980 nm. Inspired by the above results, a fast NIR-II fluorescence lifetime imaging of whole-body vascular in mice is successfully performed by using the homebuilt fluorescence lifetime imaging system, which reveals a murine abdominal capillary network with low background. A further demonstration of fluorescence lifetime multiplex imaging is carried out in molecular imaging of atherosclerosis cells and different organs in vivo through NPs conjugating with specific peptides and different injection modalities, respectively. These results demonstrate that the high PLQY NPs combined with the homebuilt fluorescence lifetime imaging system can realize a fast and high signal-to-noise fluorescence lifetime imaging; thus, opening a road for multiplex molecular imaging of atherosclerosis.

Chronic inflammation contributes to the pathogenesis of many diseases, including apparently unrelated conditions such as metabolic disorders, cardiovascular diseases, neurodegenerative diseases, osteoporosis, and tumors, but the use of conventional anti-inflammatory drugs to treat these diseases is generally not very effective given their adverse effects. In addition, some alternative anti-inflammatory medications, such as many natural compounds, have scarce solubility and stability, which are associated with low bioavailability. Therefore, encapsulation within nanoparticles (NPs) may represent an effective strategy to enhance the pharmacological properties of these bioactive molecules, and poly lactic-co-glycolic acid (PLGA) NPs have been widely used because of their high biocompatibility and biodegradability and possibility to finely tune erosion time, hydrophilic/hydrophobic nature, and mechanical properties by acting on the polymer's composition and preparation technique. Many studies have been focused on the use of PLGA-NPs to deliver immunosuppressive treatments for autoimmune and allergic diseases or to elicit protective immune responses, such as in vaccination and cancer immunotherapy. By contrast, this review is focused on the use of PLGA NPs in preclinical in vivo models of other diseases in which a key role is played by chronic inflammation or unbalance between the protective and reparative phases of inflammation, with a particular focus on intestinal bowel disease; cardiovascular, neurodegenerative, osteoarticular, and ocular diseases; and wound healing.

A reliable and automated method to segment and classify carotid artery atherosclerotic plaque components is needed to efficiently analyze multi-weighted magnetic resonance (MR) images to allow their integration into patient risk assessment for ischemic stroke. Certain plaque components such as lipid-rich necrotic core (LRNC) with hemorrhage suggest a greater likelihood of plaque rupture and stroke event. Assessment for presence and extent of LRNC could assist in directing treatment with impact upon patient outcomes.

To address the need to accurately determine the presence and extent of plaque components on carotid plaque MRI, we proposed a two-staged deep-learning-based approach that consists of a convolutional neural network (CNN), followed by a Bayesian neural network (BNN). The rationale for the two-stage network approach is to account for the class imbalance of vessel wall and background by providing an attention mask to the BNN. A unique feature of the network training was to use ground truth defined by both high-resolution ex vivo MRI data and histopathology. More specifically, standard resolution 1.5 T in vivo MR image sets with corresponding high resolution 3.0 T ex vivo MR image sets and histopathology image sets were used to define ground-truth segmentations. Of these, data from 7 patients was used for training and from the remaining two was used for testing the proposed method. Next, to evaluate the generalizability of the method, we tested the method with an additional standard resolution 3.0 T in vivo data set of 23 patients obtained from a different scanner.

Our results show that the proposed method yielded accurate segmentation of carotid atherosclerotic plaque and outperforms not only manual segmentation by trained readers, who did not have access to the ex vivo or histopathology data, but also three state-of-the-art deep-learning-based segmentation methods. Further, the proposed approach outperformed a strategy where the ground truth was generated without access to the high resolution ex vivo MRI and histopathology. The accurate performance of this method was also observed in the additional 23-patient dataset from a different scanner.

In conclusion, the proposed method provides a mechanism to perform accurate segmentation of the carotid atherosclerotic plaque in multi-weighted MRI. Further, our study shows the advantages of using high-resolution imaging and histology to define ground truth for training deep-learning-based segmentation methods.

We aimed to investigate the role and mechanism of circ_0008896 in Atherosclerosis (AS) by using oxidized low-density lipoprotein (ox-LDL)-induced human aortic endothelial cell (HAECs). Levels of genes and proteins were measured by quantitative real-time PCR and Western blot. Functional experiments, including enzyme-linked immunosorbent assay analysis, cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, tube formation assays and the detection of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) generation, were performed to investigate the role of circ_0008896 on ox-LDL-induced HAEC damage. Circ_0008896 was increased in AS patients and ox-LDL-stimulated HAECs. Functionally, circ_0008896 knockdown reversed ox-LDL-induced inflammatory response, oxidative stress, apoptosis as well as arrest of proliferation and angiogenesis in HAECs in vitro. Mechanistically, circ_0008896 functioned as a sponge for miR-188-3p to relieve the repression of miR-188-3p on its target NOD2. A series of rescue experiments showed that miR-188-3p inhibition attenuated the protective effects of circ_0008896 knockdown on ox-LDL-stimulated HAECs, and NOD2 overexpression abolished the beneficial action of miR-188-3p in the suppression of inflammatory response and oxidative stress, and the promotion of cell growth and angiogenesis in HAECs under ox-LDL treatment. Circ_0008896 silencing attenuates ox-LDL-induced inflammatory response, oxidative stress, and growth arrest in HAECs in vitro, adding further understanding for the pathogenesis of AS.

Imaging hemodynamics is crucial for the diagnosis, treatment, and prevention of vascular diseases. However, current imaging techniques are limited due to the use of ionizing radiation or contrast agents, short penetration depth, or complex and expensive data acquisition systems. Photoacoustic tomography shows promise as a solution to these issues. However, existing photoacoustic tomography methods collect signals either sequentially or through numerous detector elements, leading to either low imaging speed or high system complexity and cost. To address these issues, here we introduce a method to capture a 3D photoacoustic image of vasculature using a single laser pulse and a single-element detector that functions as 6,400 virtual ones. Our method enables ultrafast volumetric imaging of hemodynamics in the human body at up to 1 kHz and requires only a single calibration for different objects and for long-term operations. We demonstrate 3D imaging of hemodynamics at depth in humans and small animals, capturing the variability in blood flow speeds. This concept can inspire other imaging technologies and find applications such as home-care monitoring, biometrics, point-of-care testing, and wearable monitoring.

Magnetic resonance imaging (MRI)/nuclear medicine imaging (NMI) dual-modality imaging based on radiolabeled nanoparticles has been increasingly exploited for accurate diagnosis of tumor and cardiovascular diseases by virtue of high spatial resolution and high sensitivity. However, significant challenges exist in pursuing truly clinical applications, including massive preparation and rapid radiolabeling of nanoparticles. Herein, we report a clinically translatable kit for the convenient construction of MRI/NMI nanoprobes relying on the flow-synthesis and anchoring group-mediated radiolabeling (LAGMERAL) of iron oxide nanoparticles. First, homogeneous iron oxide nanoparticles with excellent performance were successfully obtained on a large scale by flow synthesis, followed by the surface anchoring of diphosphonate-polyethylene glycol (DP-PEG) to simultaneously render the underlying nanoparticles biocompatible and competent in robust labeling of radioactive metal ions. Moreover, to enable convenient and safe usage in clinics, the DP-PEG modified nanoparticle solution was freeze-dried and sterilized to make a radiolabeling kit followed by careful evaluations of its in vitro and in vivo performance and applicability. The results showed that ^99mTc labeled nanoprobes are effectively obtained with a labeling yield of over 95% in 30 minutes after simply injecting Na[^99mTcO₄] solution into the kit. In addition, the Fe₃O₄ nanoparticles sealed in the kit can well stand long-term storage even for 300 days without deteriorating the colloidal stability and radiolabeling yield. Upon intravenous injection of the as-prepared radiolabeled nanoprobes, high-resolution vascular images of mice were obtained by vascular SPECT imaging and magnetic resonance angiography, demonstrating the promising clinical translational value of our radiolabeling kit.

Objective. Automatic extraction of external elastic membrane border (EEM) and lumen-intima border (LIB) in intravascular ultrasound (IVUS) sequences aids atherosclerosis diagnosis. Existing IVUS segmentation networks ignored longitudinal relations among sequential images and neglected that IVUS images of different vascular conditions vary largely in intricacy and informativeness. As a result, they suffered from performance degradation in complicated parts in IVUS sequences.Approach. In this paper, we develop a 3D Pyramidal Densely-connected Network (PDN) with Adaptive learning and post-Correction guided by a novel cross-frame uncertainty (CFU). The proposed method is named PDN-AC. Specifically, the PDN enables the longitudinal information exploitation and the effective perception of size-varied vessel regions in IVUS samples, by pyramidally connecting multi-scale 3D dilated convolutions. Additionally, the CFU enhances the robustness of the method to complicated pathology from the frame-level (f-CFU) and pixel-level (p-CFU) via exploiting cross-frame knowledge in IVUS sequences. The f-CFU weighs the complexity of IVUS frames and steers an adaptive sampling during the PDN training. The p-CFU visualizes uncertain pixels probably misclassified by the PDN and guides an active contour-based post-correction.Main results. Human and animal experiments were conducted on IVUS datasets acquired from atherosclerosis patients and pigs. Results showed that the f-CFU weighted adaptive sampling reduced the Hausdorff distance (HD) by 10.53%/7.69% in EEM/LIB detection. Improvements achieved by the p-CFU guided post-correction were 2.94%/5.56%.Significance. The PDN-AC attained mean Jaccard values of 0.90/0.87 and HD values of 0.33/0.34 mm in EEM/LIB detection, preferable to state-of-the-art IVUS segmentation methods.

Endothelial dysfunction and inflammatory immune response trigger dedifferentiation of vascular smooth muscle cells (SMCs) from contractile to synthetic phenotype and initiate arterial occlusion. However, the complex vascular remodeling process playing roles in arterial occlusion initiation is largely unknown. We performed bulk sequencing of small and messenger RNAs in a rodent arterial injury model. Bioinformatic data analyses reveal that six miRNAs are overexpressed in injured rat carotids as well as synthetic-type human vascular SMCs. In vitro cell-based assays show that four miRNAs (miR-130b-5p, miR-132-3p, miR-370-3p, and miR-410-3p) distinctly regulate the proliferation of and monocyte adhesion to the vascular SMCs. Individual inhibition of the four selected miRNAs strongly prevents the neointimal hyperplasia in the injured rat carotid arteries. Mechanistically, miR-132-3p and miR-370-3p direct the cell cycle progression, triggering SMC proliferation. Gene ontology analysis of mRNA sequencing data consistently reveal that the miRNA targets include gene clusters that direct proliferation, differentiation, and inflammation. Notably, bone morphogenic protein (BMP)-7 is a prominent target gene of miR-370-3p, and it regulates vascular SMC proliferation in cellular and animal models. Overall, this study first reports that the miR-370-3p/BMP-7 axis determines the vascular SMC phenotype in both rodent and human systems.

Inflammation characterizes all stages of atherothrombosis and provides a critical pathophysiological link between plaque formation and its acute rupture, leading to coronary occlusion and heart attack. In the last 20 years the possibility of quantifying the degree of inflammation of atherosclerotic plaques and, therefore, also of vascular inflammation aroused much interest. ¹⁸Fluoro-deoxy-glucose photon-emissions-tomography (¹⁸F-FDG-PET) is widely used in oncology for staging and searching metastases; in cardiology, the absorption of ¹⁸F-FDG into the arterial wall was observed for the first time incidentally in the aorta of patients undergoing PET imaging for cancer staging. PET/CT imaging with ¹⁸F-FDG and ¹⁸F-sodium fluoride (¹⁸F-NaF) has been shown to assess atherosclerotic disease in its molecular phase, when the process may still be reversible. This approach has several limitations in the clinical practice, due to lack of prospective data to justify their use routinely, but it's desirable to develop further scientific evidence to confirm this technique to detect high-risk patients for cardiovascular events.

According to the American College of Cardiology/American Heart Association (ACC/AHA) new cholesterol management guidelines in 2019, statin regimen was prescribed to only about 46.4% and 30% of diabetes (DM) patients and patients with atherosclerotic cardiovascular disease (ASCVD), respectively. Atherosclerotic cardiovascular disease accounts for most deaths and disabilities in North America. This study argues that a systematic approach to identifying targeted interventions to adhere to the statin regimen for ASCVD is sparse in previous studies. This study seeks to address the research gap. Besides, the study argues that the statin regimen could improve cholesterol management with the enablers of pharmacy, providers, electronic medical records (E.M.R.), and patients. It paves the way for future research on cardiovascular and statin regimens from different perspectives. Current study has adopted the Qualitative observation method. Accordingly, the study approached the charity care primary clinic serving a large population in the northeastern part of the United States, which constitutes the project's setting. The facility has 51 internal medicine residents. The facility has E.H.R., which is used by the clinical staff. Besides, providers use electronic medication prescribing (E-Scribe). Four PDSA cycles were run in six months. Here, the interventions were intensified during each subsequent cycle. The interventions were then incorporated into routine clinical practice. Based on the observation, the study found a 25% relative improvement by six months based on the baseline data of the appropriate intensity statin prescription for patients with ASCVD or DM by medical resident trainees in our single-center primary care clinic. A total of 77% of cardiovascular disease patients were found to be on an appropriate statin dose at baseline. On the other hand, the proportion of patients with DM who were on proper dose statin was 80.4%. According to the study's findings, PDSA could result in a faster uptake and support of the ACC/AHA guidelines. Evidence indicates that overmedication of persons at low risk and time constraints are some of the most significant impediments to the greater use of prescription medications. Proactive panel management can help improve statins' use by ensuring they are used appropriately.

Atherosclerosis plaques caused by cerebrovascular and coronary artery disease have been the leading cause of death and morbidity worldwide. Precise assessment of the degree of atherosclerotic plaque is critical for predicting the risk of atherosclerosis plaques and monitoring postinterventional outcomes. However, traditional imaging techniques to predict cardiocerebrovascular events mainly depend on quantifying the percentage reduction in luminal diameter, which would immensely underestimate non-stenotic high-risk plaque. Identifying the degree of atherosclerosis plaques still remains highly limited. vNanomedicine-based imaging techniques present unique advantages over conventional techniques due to the superior properties intrinsic to nanoscope, which possess enormous potential for characterization and detection of the features of atherosclerosis plaque vulnerability. Here, we review recent advancements in the development of targeted nanomedicine-based approaches and their applications to atherosclerosis plaque imaging and risk stratification. Finally, the challenges and opportunities regarding the future development and clinical translation of the targeted nanomedicine in related fields are discussed.

The poor generalizability of intravascular ultrasound (IVUS) analysis methods caused by the great diversity of IVUS datasets is hopefully addressed by the domain adaptation strategy. However, existing domain adaptation models underperform in intravascular structural preservation, because of the complex pathology and low contrast in IVUS images. Losing structural information during the domain adaptation would lead to inaccurate analyses of vascular states. In this paper, we propose a Multilevel Structure-Preserved Generative Adversarial Network (MSP-GAN) for transferring IVUS domains while maintaining intravascular structures. On the generator-discriminator baseline, the MSP-GAN integrates the transformer, contrastive restraint, and self-ensembling strategy, for effectively preserving structures in multi-levels, including global, local, and fine levels. For the global-level pathology maintenance, the generator explores long-range dependencies in IVUS images via an incorporated vision transformer. For the local-level anatomy consistency, a region-to-region correspondence is forced between the translated and source images via a superpixel-wise multiscale contrastive (SMC) constraint. For reducing distortions of fine-level structures, a self-ensembling mean teacher generates the pixel-wise pseudo-label and restricts the translated image via an uncertainty-aware teacher-student consistency (TSC) constraint. Experiments were conducted on 20 MHz and 40 MHz IVUS datasets from different medical centers. Ablation studies illustrate that each innovation contributes to intravascular structural preservation. Comparisons with representative domain adaptation models illustrate the superiority of the MSP-GAN in the structural preservation. Further comparisons with the state-of-the-art IVUS analysis accuracy demonstrate that the MSP-GAN is effective in enlarging the generalizability of diverse IVUS analysis methods and promoting accurate vessel and lumen segmentation and stenosis-related parameter quantification.

The association between white blood cell (WBC) count and arterial stiffness in patients with hypertension is not well-documented. We aimed to examine the relationships of total WBC count with arterial stiffness and risk of macrovascular damage in hypertensive patients. A total of 631 hypertensive adults (mean age: 65.6 years) were included in the present study. Arterial stiffness was determined by brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). Macrovascular damage was defined as baPWV >1.8 m/s or ABI <.9. The dose-response associations were assessed by multivariate linear or logistic regression models. After multivariate adjustments, we observed a dose-response relationship between increasing total WBC count and arterial stiffness. Participants in the highest tertile of total WBC count showed a significantly elevated baPWV (β = .088; 95% CI: .021, .154; P_trend = .010) and reduced ABI (β = -.027; 95% CI: -.046, -.008; P_trend = .005), as compared with those in the first tertile. The association was similar in different subgroups. In addition, elevated total WBC count was related to a greater risk of macrovascular damage, as indicated by baPWV >1.8 m/s (OR = 1.86; 95% CI: 1.15, 2.99, comparing the extreme tertiles). Our data suggest that elevated total WBC count was related to arterial stiffness among individuals with hypertension.

There is an urgent need for contrast agents to detect the first inflammation stage of atherosclerosis by cardiovascular optical coherence tomography (CV-OCT), the imaging technique with the highest spatial resolution and sensitivity of those used during coronary interventions. Gold nanoshells (GNSs) provide the strongest signal by CV-OCT. GNSs are functionalized with the cLABL peptide that binds specifically to the ICAM-1 molecule upregulated in the first stage of atherosclerosis. Dark field microscopy and CV-OCT are used to evaluate the specific adhesion of these functionalized GNSs to activated endothelial cells. This adhesion is investigated under static and dynamic conditions, for shear stresses comparable to those of physiological conditions. An increase in the scattering signal given by the functionalized GNSs attached to activated cells is observed compared to non-activated cells. Thus, cLABL-functionalized GNSs behave as excellent contrast agents for CV-OCT and promise a novel strategy for clinical molecular imaging of atherosclerosis.