Cardiovascular diseases (CVDs) represent a profound challenge with inflammation playing a significant role in their pathophysiology. Extracellular vesicles (EVs), which are membranous structures encapsulated by a lipid bilayer, are essential for intercellular communication by facilitating the transport of specific bioactive molecules, including microRNAs, proteins, and lipids. Emerging evidence suggests that the regulatory mechanisms governing cardiac resident cells are influenced by EVs, which function as messengers in intercellular communication and thereby contribute to the advancement of CVDs. In this review, we discuss the multifaceted biological functions of EVs and their involvement in the pathogenesis of various CVDs, encompassing myocardial infarction, ischemia-reperfusion injury, heart failure, atherosclerosis, myocarditis, cardiomyopathy, and aneurysm. Furthermore, we summarize the recent advancements in utilizing EVs as non-invasive biomarkers and in cell-free therapy based on EVs for the diagnosis and treatment of CVDs. Future research should investigate effective techniques for the isolation and purification of EVs from body fluids, while also exploring the pathways for the clinical translation of therapy based on EVs. Additionally, it is imperative to identify appropriate EV-miRNA profiles or combinations present in the circulation of patients, which could serve as biomarkers to improve the diagnostic accuracy of CVDs. By synthesizing and integrating recent research findings, this review aims to provide innovative perspectives for the pathogenesis of CVDs and potential therapeutic strategies.

Sepsis-induced cardiomyopathy (SICM) is a complex and fatal manifestation of sepsis, characterised by myocardial dysfunction that exacerbates the clinical prognosis in septic patients. While the pathophysiology of SICM remains incompletely understood, emerging evidence highlights the multifaceted functions of exosomes, small membrane-bound extracellular vesicles, in mediating the inflammatory responses and cardiac dysfunction involved in this condition. During sepsis, exosomes are secreted by various cells, such as cardiomyocytes, endothelial cells and macrophages, which serve as critical messengers, transferring proteins, lipids and RNA molecules that influence recipient cells, thus affecting cellular functions and disease progression. This review summarises the pathophysiology of SICM and the basics of exosomes and focuses on exosome-mediated mechanisms in SICM, including their role in inflammation, oxidative stress, mitochondrial dysfunction and myocardial injury, offering novel insights into the exosome-based therapeutic strategies in SICM.

Exosomes, small extracellular vesicles ranging from 30 to 150 nanometers in diameter, have emerged as pivotal mediators of intercellular communication. These vesicles, originally perceived as cellular debris, are now recognized for their intricate roles in transporting bioactive molecules, including proteins, lipids, and nucleic acids, between cells. Exosomes have received considerable attention due to their roles in diverse physiological and pathological processes, especially in relation to cardiovascular diseases (CVDs). CVDs are intricately linked, sharing common risk factors and pathological mechanisms, such as inflammation, oxidative stress, and endothelial dysfunction. Exosomes have been implicated in either directly or indirectly influencing these phenomena. They are secreted by virtually all cell types, including endothelial cells, cardiomyocytes, and stem cells, play critical roles in maintaining vascular homeostasis and responding to pathological stimuli. Their capacity to traverse biological barriers, maintain stability in circulation, and effectively encapsulate and deliver a variety of molecular cargos makes them promising candidates for both biomarkers and therapeutic agents. This review aims to explore the multifaceted roles of exosomes in CVDs. And we will discuss the mechanisms of exosome biogenesis and release, their molecular composition, and the ways in which they contribute to disease pathophysiology. Additionally, we will emphasize the potential of exosomes as diagnostic biomarkers and their therapeutic uses, highlighting their significance in the advancement of innovative treatment strategies. This review explores recent findings and advancements in exosome research, emphasizing their significance in CVD and paving the way for future studies and clinical applications.

The polarization of microglia promotes the development of cisplatin-induced ototoxicity, and exosomes (Exo) derived from TNF-α preconditioned mesenchymal stem cells (MSCs) may induce the polarization of macrophage. Mice were intraperitoneally injected with cisplatin to establish the ototoxicity model. Bone marrow MSCs (BMSCs) were preconditioned with TNF-α for 48 h, and the relevant TNF-Exo or Exo was enriched, which were further trans-tympanically administered in the left ear of ototoxic mice. Auditory sensitivity was revealed with auditory brainstem response (ABR) at 8, 16, 24, and 32 kHz. The number of hair cells was detected with Myosin 7a staining. Damaged auditory sensitivity and up-regulated hair cell loss were revealed in cisplatin-exposed mice, which could be reversed by Exo or TNF-Exo treatment. Mechanically, up-regulated Iba1, Cd86, iNOS, Cd206, and Arg1 were detected in cisplatin-exposed cochlea. TNF-Exo or Exo administration further decreased Iba1, Cd86, and iNOS expression, and increased cd206 and Arg1 expression. TNF-Exo or Exo administration inhibited the productin of pro-inflammatory cytokines (IL-1β and IL-6), while enhanced the anti-inflammatory cytokine IL-10 production in the cisplatin-exposed cochlea. Importantly, TNF-Exo administration showed more profound benefits compared with Exo. TNF-α preconditioning might be a new therapeutic option to enhance the capability of BMSCs-derived exosomes against cisplatin-induced ototoxicity.

Probiotic bacteria are normal inhabitants of a healthy human gut, conferring multiple beneficial effects on the gut and beyond. Under various disease states, the abundance and diversity of beneficial bacteria are significantly decreased, a process called dysbiosis. Among the intra- and extracellular components of probiotics, the extracellular vesicles (EVs) secreted by them have recently garnered significant attention as potential mediators of probiotics' effects on host health. Further, these nanosized particles that encapsulate a wide range of bioactive molecules (proteins, lipids, RNA, and DNA) are standing out as key factors that could mediate gut microbiota-host communication and confer ameliorating effects in experimental inflammatory, metabolic, and cardiovascular disease models. However, a standard protocol of EV isolation from probiotic bacteria, not varying from lab to lab, must be established to achieve consistency in the experimental results in these pre-clinical models. Our current study compared two commonly used methods for EV isolation from biological samples, ultracentrifugation and precipitation, to develop a standard protocol for isolating EVs from the probiotics Lactobacillus acidophilus (LA), a Gram-positive bacterium, and Escherichia coli Nissle (EcN), a Gram-negative bacterium. The ultracentrifugation method gave ~1.5-fold higher EV yield for both LA and EcN compared to the precipitation method. Further, EcN released a higher level of EVs compared to LA. EVs were quantified and characterized by nanoparticle-tracking analysis (NTA) and by measuring the specific surface biomarkers using Western blot. Here, we describe our standardized step-by-step protocol for isolating EVs from probiotic bacteria and their characterization.

Extracellular vesicles (EVs) are nanosized particles secreted by cells that play crucial roles in intercellular communication, especially in the context of cardiovascular diseases (CVDs). These vesicles carry complex cargo, including proteins, lipids, and nucleic acids, that reflects the physiological or pathological state of their cells of origin. Multiomics analysis of cell-derived EVs has provided valuable insights into the molecular mechanisms underlying CVDs by identifying specific proteins and EV-bound targets involved in disease progression. Recent studies have demonstrated that engineered EVs, which are designed to carry specific therapeutic molecules or modified to enhance their targeting capabilities, hold promise for treating CVDs. Analysis of the EV proteome has been instrumental in identifying key proteins that can be targeted or modulated within these engineered vesicles. For example, proteins involved in inflammation, thrombosis, and cardiac remodeling have been identified as potential therapeutic targets. Furthermore, the engineering of EVs to increase their delivery to specific tissues, such as the myocardium, or to modulate their immunogenicity and therapeutic efficacy is an emerging area of research. By leveraging the insights gained from multiomics analyses, researchers are developing EV-based therapies that can selectively target pathological processes in CVDs, offering a novel and potentially more effective treatment strategy. This review integrates the core findings from EV multiomics analysis in the context of CVDs and highlights the potential of engineered EVs in therapeutic applications.

In this editorial we comment on the article by Safwan M et al. We especially focused on the cardiac function restoration by the use of mesenchymal stem cells (MSCs) therapy for heart failure (HF), which has emerged as a new treatment approach as "Living Biodrugs". HF remains a significant clinical challenge due to the heart's inability to pump blood effectively, despite advancements in medical and device-based therapies. MSCs have emerged as a promising therapeutic approach, offering benefits beyond traditional treatments through their ability to modulate inflammation, reduce fibrosis, and promote endogenous tissue regeneration. MSCs can be derived from various tissues, including bone marrow and umbilical cord. Umbilical cord-derived MSCs exhibit superior expansion capabilities, making them an attractive option for HF therapy. Conversely, bone marrow-derived MSCs have been extensively studied for their potential to improve cardiac function but face challenges related to cell retention and delivery. Future research is focusing on optimizing MSC sources, enhancing differentiation and immune modulation, and improving delivery methods to overcome current limitations.

Extracellular vesicles (EVs) are important mediators of intercellular communication within the cardiovascular system, playing essential roles in physiological homeostasis and contributing to the pathogenesis of various cardiovascular diseases (CVDs). However, their potential as diagnostic biomarkers and therapeutic agents in rare cardiovascular diseases, such as valvular heart disease (VHD) and cardiomyopathies, remains largely unexplored. This review comprehensively emphasizes recent advancements in extracellular vesicle research, explicitly highlighting their growing significance in diagnosing and potentially treating rare cardiovascular diseases, with a particular focus on valvular heart disease and cardiomyopathies. We highlight the potential of extracellular vesicle-based liquid biopsies as non-invasive tools for early disease detection and risk stratification, showcasing specific extracellular vesicle-associated biomarkers (proteins, microRNAs, lipids) with diagnostic and prognostic value. Furthermore, we discussed the therapeutic promise of extracellular vesicles derived from various sources, including stem cells and engineered extracellular vesicles, for cardiac repair and regeneration through their ability to modulate inflammation, promote angiogenesis, and reduce fibrosis. By integrating the findings and addressing critical knowledge gaps, this review aims to stimulate further research and innovation in extracellular vesicle-based diagnostics and therapeutics of cardiovascular disease.

Extracellular vesicles (EVs) are involved in both physiological and pathological processes in many organ systems and are essential in mediating intercellular communication and maintaining organismal homeostasis. It is helpful to propose new strategies for disease treatment by elucidating the mechanisms of EV release and sorting. An increasing number of studies have shown that there is specific homeostasis in EVs, which is helpful for the human body to carry out physiological activities. In contrast, an EV homeostasis im-balance promotes or accelerates disease onset and development. Alternatively, regulating the quality of EVs can maintain homeostasis and even achieve the purpose of treating conditions. An analysis of the role of EV homeostasis in the onset and development of cardiovascular disease is presented in this review. This article also summarizes the methods that regulate EV homeostasis and their application in cardiovascular diseases. In particular, this study focuses on the connection between EV steady states and the cardiovascular system and the potential value of EVs in treating cardiovascular diseases.

Cardiovascular complications are the most deadly and cost-driving effects of diabetes mellitus (DM). One of them, which is steadily attracting attention among scientists, is diabetes-induced heart failure, also known as diabetic cardiomyopathy (DCM). Despite significant progress in the research concerning the disease, a universally accepted definition is still lacking. The pathophysiology of the processes accelerating heart insufficiency in diabetic patients on molecular and cellular levels also remains elusive. However, the recent interest concerning extracellular vesicles (EVs) has brought promise to further clarifying the pathological events that lead to DCM. In this review, we sum up recent investigations on the involvement of EVs in DCM and show their therapeutic and indicatory potential.

Mesenchymal stem cells (MSCs) have important research value and broad application prospects in cardiovascular diseases (CVDs). However, few bibliometric analyses on MSCs in cardiovascular diseases are available. This study aims to provide a thorough review of the cooperation and influence of countries, institutions, authors, and journals in the field of MSCs in cardiovascular diseases, with the provision of discoveries in the latest progress, evolution paths, frontier research hotspots, and future research trends in the regarding field.

The articles related to MSCs in cardiovascular diseases were retrieved from the Web of Science. The bibliometric study was performed by CiteSpace and VOSviewer, and the knowledge map was generated based on data obtained from retrieved articles.

In our study, a total of 4,852 publications launched before August 31, 2023 were accessed through the Web of Science Core Collection (WoSCC) database via our searching strategy. Significant fluctuations in global publications were observed in the field of MSCs in CVDs. China emerged as the nation with the largest number of publications, yet a shortage of high-quality articles was noted. The interplay among countries, institutions, journals and authors is visually represented in the enclosed figures. Importantly, current research trends and hotspots are elucidated. Cluster analysis on references has highlighted the considerable interest in exosomes, extracellular vesicles, and microvesicles. Besides, keywords analysis revealed a strong emphasis on myocardial infarction, therapy, and transplantation. Treatment methods-related keywords were prominent, while keywords associated with extracellular vesicles gathered significant attention from the long-term perspective.

MSCs in CVDs have become a topic of active research interest, showcasing its latent value and potential. By summarizing the latest progress, identifying the research hotspots, and discussing the future trends in the advancement of MSCs in CVDs, we aim to offer valuable insights for considering research prospects.

Despite the great progress in diagnosis, prevention, and treatment, cardiovascular diseases (CVDs) are still the most prominent cause of death worldwide [...].

Cancer disease is the second leading cause of death worldwide. In 2023, about 2 million new cancer cases and 609,820 cancer deaths are projected to occur in the United States. The driving forces of cancer progression and metastasis are widely varied and comprise multifactorial events. Although there is significant success in treating cancer, patients still present with tumors at advanced stages. Therefore, the discovery of novel oncologic pathways has been widely developed. Tumor cells communicate with each other through small extracellular vesicles (sEVs), which contribute to tumor-stromal interaction and promote tumor growth and metastasis. sEV-specific inhibitors are being investigated as a next-generation cancer therapy. A literature search was conducted to discuss different options for targeting sEV pathways in cancer cells. However, there are some challenges that need to be addressed in targeting sEVs: i) specificity and toxicity of sEV inhibitor, ii) targeted delivery of sEV inhibitors, iii) combination of sEV inhibitors with current standard chemotherapy to improve patients' clinical outcomes, and iv) data reproducibility and applicability at distinct levels of the disease. Despite these challenges, sEV inhibitors have immense potential for effectively treating cancer patients.

Myocardial infarction (MI) and its associated poor prognosis pose significant risks to human health. Nanomaterials hold great potential for the treatment of MI due to their targeted and controlled release properties, particularly biomimetic nanomaterials. The utilization of biomimetic strategies based on extracellular vesicles (EVs) and cell membranes will serve as the guiding principle for the development of nanomaterial therapy in the future. In this review, we present an overview of research progress on various exosomes derived from mesenchymal stem cells, cardiomyocytes, or induced pluripotent stem cells in the context of myocardial infarction (MI) therapy. These exosomes, utilized as cell-free therapies, have demonstrated the ability to enhance the efficacy of reducing the size of the infarcted area and preventing ischaemic reperfusion through mechanisms such as oxidative stress reduction, polarization modulation, fibrosis inhibition, and angiogenesis promotion. Moreover, EVs can exert cardioprotective effects by encapsulating therapeutic agents and can be engineered to specifically target the infarcted myocardium. Furthermore, we discuss the use of cell membranes derived from erythrocytes, stem cells, immune cells and platelets to encapsulate nanomaterials. This approach allows the nanomaterials to camouflage themselves as endogenous substances targeting the region affected by MI, thereby minimizing toxicity and improving biocompatibility. In conclusion, biomimetic nano-delivery systems hold promise as a potentially beneficial technology for MI treatment. This review serves as a valuable reference for the application of biomimetic nanomaterials in MI therapy and aims to expedite the translation of NPs-based MI therapeutic strategies into practical clinical applications.

Ischemic heart disease, a leading cause of death worldwide, manifests clinically as myocardial infarction. Contemporary therapies using mesenchymal stromal cells (MSCs) and their derivative (exosomes, EXOs) were developed to decrease the progression of cell damage during ischemic injury. Laminin alpha 2 (LAMA2) is an important extracellular matrix protein of the heart. Here, we generated MSC-derived exosomes cultivated under LAMA2 coating to enhance human-induced pluripotent stem cell (hiPSC)-cardiomyocyte recognition of LAMA2-EXOs, thus, increasing cell protection during ischemia reoxygenation. We mapped the mRNA content of LAMA2 and gelatin-EXOs and identified 798 genes that were differentially expressed, including genes associated with cardiac muscle development and extracellular matrix organization. Cells were treated with LAMA2-EXOs 2 h before a 4 h ischemia period (1% O2, 5% CO2, glucose-free media). LAMA2-EXOs had a two-fold protective effect compared to non-treatment on plasma membrane integrity and the apoptosis activation pathway; after a 1.5 h recovery period (20% O2, 5% CO2, cardiomyocyte-enriched media), cardiomyocytes treated with LAMA2-EXOs showed faster recovery than did the control group. Although EXOs had a protective effect on endothelial cells, there was no LAMA2-enhanced protection on these cells. This is the first report of LAMA2-EXOs used to treat cardiomyocytes that underwent ischemia-reoxygenation injury. Overall, we showed that membrane-specific EXOs may help improve cardiomyocyte survival in treating ischemic cardiovascular disease.