bims-evecad 2025-10-19 papers

Issue of 2025–10–19
five papers selected by
Cliff Dominy

Med Sci Monit. 2025 Oct 15. 31 e948948

Extracellular Vesicles as Emerging Regulators in Ischemic and Hypertrophic Cardiovascular Diseases: A Review of Pathogenesis and Therapeutics.

Min Chen, Yanming Wu, Cheng Chen.

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, have emerged as important regulators in specific cardiovascular conditions such as myocardial infarction, atherosclerosis, coronary artery disease, and cardiac hypertrophy. EVs mediate intercellular communication by transferring bioactive cargo such as proteins, lipids, and nucleic acids. EVs influence crucial pathological processes, including inflammation, fibrosis, apoptosis, and cardiac remodeling, contributing to disease progression. This review assessed the therapeutic potential of stem cell-derived EVs in reducing inflammation, enhancing angiogenesis, modulating immune responses, and mitigating cardiac remodeling. Specific EV-derived miRNAs such as miR-146a, miR-181b, and miR-21 exhibited beneficial effects in promoting cardiac repair, reducing fibrosis, and improving cardiac function after injury. Special focus is placed on stem cell-derived EVs, which show promise in reducing myocardial injury, promoting angiogenesis, and attenuating pathological hypertrophy. Moreover, we explore the emerging concept of EVs as biomarkers, with circulating endothelial- and platelet-derived EVs correlating with vascular dysfunction, plaque instability, and pro-coagulant activity in clinical studies. Despite their therapeutic promise, the clinical translation of EV-based strategies faces challenges, including lack of standardized isolation protocols, heterogeneity of EV subpopulations, and limited in vivo targeting specificity. Addressing these barriers will be essential to harness EVs as next-generation diagnostic tools and cell-free therapeutic agents. This article reviews the emerging roles of extracellular vesicles, including exosomes, microvesicles, and apoptotic bodies, in atherosclerosis, myocardial ischemia, infarction and reperfusion injury, and cardiac hypertrophy.

DOI: https://doi.org/10.12659/MSM.948948

J Cardiovasc Transl Res. 2025 Oct 11.

Extracellular Vesicles in Cardiovascular Diseases: Signaling, Biomarker, and Therapy.

Wenxi Chen, Xinyi Zhu, Shuo Yu, Hong Ma.

Cardiovascular diseases (CVDs) remain the global leading cause of mortality, necessitating novel diagnostics and therapies. Extracellular vesicles (EVs)-including exosomes, microvesicles, and apoptotic bodies-serve as key intercellular communicators in cardiovascular system. As carriers of bioactive miRNAs/proteins, EVs regulate inflammation, fibrogenesis, angiogenesis, and cardiac/systemic communication. Their non-invasive accessibility and disease-specific molecular signatures enable diagnostic applications. Endogenous origin and targeting capacity make EV ideal drug delivery platforms, while engineering of surface/content properties enhances their therapeutic specificity. However, key challenges persist in reproducibility, long-term safety profiles, clearance mechanisms, and therapeutic applications. Therefore, we highlight the potential of EVs as engineered drug carriers and their therapeutic promise for CVDs such as myocardial infarction, atherosclerosis, and heart failure. Future clinical translation of EV-based tools offers transformative potential-from cardiovascular diagnostics to regenerative therapies-where collaborative efforts will accelerate the pipeline development of these emerging solutions for clinical CVDs management.

Keywords: Cardiovascular diseases; Clinical translation; Extracellular vesicles; Interorgan crosstalk

DOI: https://doi.org/10.1007/s12265-025-10706-y

Arterioscler Thromb Vasc Biol. 2025 Oct 16.

Extracellular Vesicles From Chylomicron-Treated Endothelial Cells Drive Macrophage Inflammation.

Anna Tilp, Dimitris Nasias, Andrew L Carley, Min Young Park, Ashley Mooring, Munichandra Babu Tirumalasetty, Nada A Abumrad, Yang Wang, Qing Robert Miao, E Douglas Lewandowski, José O Alemán, Ira J Goldberg, Ainara G Cabodevilla.

BACKGROUND: Movement of circulating lipids into tissues and arteries requires transfer across the endothelial cell (EC) barrier. This process allows the heart to obtain fatty acids, its chief source of energy, and apoB-containing lipoproteins to cross the arterial endothelial barrier, leading to cholesterol accumulation in the subendothelial space. Multiple studies have established elevated postprandial TRLs (triglyceride-rich lipoproteins) as an independent risk factor for cardiovascular disease. We explored how chylomicrons affect ECs and transfer their fatty acids across the EC barrier.
METHODS: We had reported that media from chylomicron-treated ECs lead to lipid droplet formation in macrophages. To determine the responsible component of this media, we assessed whether removing the extracellular vesicles (EVs) would obviate this effect. EVs from control and treated cells were then characterized by protein, lipid, and microRNA content. We also studied the EV-induced transcription changes in macrophages and ECs and whether knockdown of SR-BI (scavenger receptor-BI) altered these responses. In addition, using chylomicrons labeled with [13C]oleate, we studied the uptake and release of this labeled by ECs.
RESULTS: Chylomicron treatment of ECs led to an inflammatory response that included production of EVs that drove macrophage lipid droplet accumulation. The EVs contained little free fatty acids and triglycerides, but abundant phospholipids and diacylglycerols. In concert with this, [13]C labeled chylomicron triglycerides exited ECs primarily in phospholipids. EVs from chylomicron-treated versus untreated ECs were larger, more abundant, and contained specific microRNAs. Treatment of macrophages and naive ECs with media from chylomicron-treated ECs increased expression of inflammatory genes.
CONCLUSIONS: EC chylomicron metabolism produces EVs that increase macrophage inflammation and create LDs. Media containing these EVs also increases EC inflammation, illustrating an autocrine inflammatory process. Fatty acids within chylomicron triglycerides are converted to phospholipids within EVs. Thus, EC uptake of chylomicrons constitutes an important pathway for vascular inflammation and tissue lipid acquisition.

Keywords: cardiovascular diseases; chylomicrons; endothelial cells; inflammation; macrophages

DOI: https://doi.org/10.1161/ATVBAHA.125.322712

iScience. 2025 Oct 17. 28(10): 113529

Multicomponent-based analyses of ACS-patient-derived extracellular vesicles as likely tools for tailored interventional approaches.

Saveria Femminò, Alessandro Sarcinella, Alberto Grosso, Francesca Mensitieri, Ovidio De Filippo, Francesco Bruno, Albino Coglianese, Marta Tapparo, Edoardo Pace, Sharad Kholia, Stefania Bruno, Rosa Ciullo, Fabrizio Buffolo, Giovanni Camussi, Gaetano Maria De Ferrari, Fabrizio Dal Piaz, Fabrizio D'Ascenzo, Maria Felice Brizzi.

Reliable predictive biomarkers to reduce unnecessary coronary angiograms (CAGs) in non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina (UA) patients displaying high-risk features are still lacking. Here, we show that profiling patient-derived circulating extracellular vesicles (EVs) can not only improve their risk stratification but also reduce unnecessary CAGs. Analysis of EVs and their miR cargo revealed that CD62p+EVs enriched in miR-130a-3p correlated with the absence of non-critical coronary artery disease (CAD). Proteomic analysis identified nine proteins differentially enriched in patients with or without critical-CAD (NO CAD), irrespective of their diagnosis. Multivariate analysis identified miR-130a-3p (odds ratio [OR]:0.35 [0.19-0.67]), phospholipid transfer protein (OR 0.96 [0.94-0.98]), and subunit beta of mitochondrial trifunctional enzyme (OR:0.96 [0.94-0.98]) as predictors of NO CAD. Furthermore, EV-miR-130a-3p enrichment predicted the absence of multivessel disease (OR:0.46 [0.23-0.90]). These findings establish EV profiling as a valuable tool for stratifying and optimizing the clinical management of patients with acute coronary syndrome.

Keywords: Cardiovascular medicine; Proteomics

DOI: https://doi.org/10.1016/j.isci.2025.113529

Mol Med Rep. 2026 Jan;pii: 5. [Epub ahead of print]33(1):

Role and relevance of exosome-mediated epigenetic regulation in the pathogenesis, diagnosis and treatment of cardiovascular diseases (Review).

Yishuo Zhang, Shanshan Zhang, Yijing Li, Wenqi Jin, Liya Zhou, Jing Lu.

Cardiovascular diseases (CVDs) are among the main factors impacting negatively human health on a global scale. Every year, there is an increase in the prevalence of CVDs despite advancements in therapy for managing traditional risk factors. Research on exosomes is has garnered great interest due to their role in regulating intercellular communication. Exosome‑mediated epigenetic regulation is involved in the interaction between circulating cells and blood arteries, as well as in intercellular communication processes, and exosomes serve as biomarkers of cell activation. The present study aimed to summarize the recent research on exosome‑mediated epigenetic regulation mechanisms, as well as the roles of exosomes in the pathology and diagnosis of CVDs, which may increase the current understanding of the precise functions that exosomes play in the development of CVDs.

Keywords: cardiovascular diseases; diagnosis and treatment; epigenetic regulation; exosomes; mechanism

DOI: https://doi.org/10.3892/mmr.2025.13715