bims-evecad 2026-09-13 papers

Issue of 2026–09–13
six papers selected by
Cliff Dominy

J Cardiovasc Transl Res. 2026 Sep 09. pii: 114. [Epub ahead of print]19(1):

The Role and Mechanism of Endothelial Progenitor Cell-Derived Extracellular Vesicles in Vascular Repair of Ischemic Heart Disease.

Qiling Han, Xinmei Wang, Houjin Zhao.

Ischemic heart disease (IHD) remains a leading global cause of death, sustained by microvascular dysfunction and defective endogenous repair despite revascularization. Endothelial progenitor cells (EPCs) were initially proposed as regenerative mediators, but direct cell therapy is constrained by poor engraftment, phenotypic heterogeneity, and safety concerns. Accumulating evidence establishes EPC-derived extracellular vesicles (EPC-EVs) as the principal effectors of vascular repair. These vesicles deliver bioactive cargo-including miR-126, miR-210, lncRNAs, and proteins that activate VEGF/PI3K/AKT/eNOS signaling in endothelial cells, promote angiogenesis and endothelial survival, attenuate apoptosis and ferroptosis, and induce reparative M2 macrophage polarization. Compared with cell therapy, EPC-EVs offer superior stability, lower immunogenicity, and manufacturing control as a cell-free platform. Translational challenges persist, including inconsistent EPC definitions, isolation variability, absence of validated potency assays linked to cardiovascular endpoints, and limited long-term safety data. Engineering strategies such as hypoxic preconditioning and targeted delivery may facilitate clinical translation of EPC-EV therapy for IHD.

Keywords: Angiogenesis; Endothelial Progenitor Cells; Extracellular Vesicles; Ischemic Heart Disease; Vascular Repair

DOI: https://doi.org/10.1007/s12265-026-10822-3

Cardiovasc Drugs Ther. 2026 Sep 05.

Spatiotemporal Nanotherapy After Myocardial Infarction: Targeting the Inflammatory-to-reparative Transition With Extracellular Vesicles and Engineered Nanoparticles.

Xuesi Chen, Yingchun Bao, Qijun Zhang.

PURPOSE: Post-myocardial infarction (MI) healing is a moving sequence of injury, inflammatory clearance, resolution, vascular repair, and scar maturation. This review evaluates how extracellular vesicles (EVs), cell-derived nanovesicles, and engineered nanoparticles can be matched to these changing biological requirements.
METHODS: A critical narrative synthesis was organized around four approximate post-MI windows: minutes to 24 h, days 1-3, days 3-7, and after day 7. Representative mechanistic, rodent, porcine, and human studies were compared by target cell, cargo, material, release profile, route, quantitative delivery evidence, efficacy, and translational liability.
RESULTS: Early oxidative and microvascular injury favors brief cytoprotection and vascular targeting; the inflammatory peak favors calibrated control of recruited leukocytes while preserving debris removal; resolution favors efferocytosis, reparative immune signaling, angiogenesis, and local immunomodulation; and later remodeling favors selective rather than global antifibrotic therapy. Directly generated nanovesicles and modified-mRNA lipid nanoparticles expand the design space. However, human evidence remains sparse, and most preclinical studies use fixed schedules, young non-comorbid rodents, qualitative biodistribution, and incompletely defined potency assays.
CONCLUSION: A credible spatiotemporal product must demonstrate phase-dependent target availability, controlled exposure, target-cell cargo engagement, and reduced benefit or emerging harm with a deliberately mismatched schedule. Translation requires quantitative pharmacokinetics and biodistribution, route-specific safety, mechanism-linked potency, scalable manufacturing, and validation in reperfused comorbid large-animal models.

Keywords: Cardiac remodeling; Drug delivery; Extracellular vesicles; Inflammation resolution; Myocardial infarction; Nanoparticles

DOI: https://doi.org/10.1007/s10557-026-07950-y

Ren Fail. 2026 Dec;48(1): 2727298

Mitochondrial extracellular vesicles in cardiorenal syndrome: emerging mediators of mitochondrial signaling and inter-organ crosstalk.

Jian Hou, Xiaozhi Yang, Rui Zheng, Jianhao Li, Dayu Wang, Bo Hu, Xin Jin, Guangtao Xu.

Cardiorenal syndrome (CRS) comprises five clinically distinct patterns of acute, chronic, or systemic heart-kidney interaction. Mitochondrial dysfunction is shared by cardiac and renal injury, but the cardiorenal setting is distinguished by the possibility that mitochondrial stress arising in one organ is externalized and transmitted to the other. Extracellular vesicles (EVs) are established mediators of intercellular communication, and EVs carrying mitochondrial DNA, proteins, lipids, RNA, or structurally preserved mitochondrial material-collectively referred to here as mitochondrial extracellular vesicles (mitoEVs)-may connect mitochondrial quality control with systemic signaling. Direct CRS-specific evidence, however, remains limited: patient-derived studies support pathogenic effects of total circulating EVs, whereas most mitoEV-specific mechanisms are inferred from related cardiovascular, renal, inflammatory, cancer, or regenerative models. Accordingly, this review presents an evidence-graded conceptual framework rather than a definitive mechanistic summary. We define and classify mitoEVs, outline methodological requirements for their isolation, same-particle identification, cargo-topology analysis, quantification, and functional validation, and map the available evidence across the five CRS subtypes. We further propose the mitoEV-mitophagy-inflammation axis as a working hypothesis in which impaired mitochondrial quality control may favor vesicular export, inflammatory activation in recipient cells, and secondary mitochondrial dysfunction. Finally, we evaluate the biomarker and therapeutic potential of mitoEVs while emphasizing the need for subtype-specific clinical validation, standardized analytical workflows, source-resolved studies, and rigorous distinction between pathological and reparative vesicle populations.

Keywords: Cardiorenal syndrome; inter-organ communication; mitochondrial DNA; mitochondrial dysfunction; mitochondrial extracellular vesicles

DOI: https://doi.org/10.1080/0886022X.2026.2727298

Clin Transl Gastroenterol. 2026 Sep 09.

The Role and Therapeutic Potential of Gut Microbiota and Their Extracellular Vesicles in Neurological, Cardiovascular, and Metabolic Diseases.

Zhirong Rao, Linwei Li, Ying Liang, Xiaotian Huang, Qiong Liu.

Gut microbiota-derived extracellular vesicles (EVs) have emerged as important mediators of host-microbiota communication, influencing physiological and pathological processes across multiple organ systems through gut-organ axes. These nanoscale vesicles can exert either protective or pathogenic effects depending on their microbial origin, molecular cargo, and host context. Increasing evidence suggests that microbiota-derived EVs contribute to the pathogenesis of neurological, cardiovascular, and metabolic disorders by modulating immune, inflammatory, and metabolic pathways. In addition, their stability, accessibility in biological fluids, and capacity for targeted delivery have generated interest in their use as diagnostic biomarkers and therapeutic platforms. In this narrative review, we summarize current evidence regarding the role of gut microbiota-derived EVs in representative neurological, cardiovascular, and metabolic diseases, highlighting both their detrimental and beneficial effects. We further discuss their translational potential, current challenges in clinical application, and emerging strategies for EV-based diagnostics and therapeutics. Collectively, this review provides a conceptual and translational framework for advancing microbiota-derived EV research toward clinical practice.

Keywords: Biomarkers; Gut microbiota-derived extracellular vesicles; Gut-organ axes; Therapeutic potential; Translational medicine

DOI: https://doi.org/10.14309/ctg.0000000000001101

Sci Adv. 2026 Sep 11. 12(37): eaef1504

AT1R-mediated NIR-II/PA imaging-guided iCM exosome therapy for myocardial ischemia revascularization.

Lu Wang, Xinkui Zhang, Haotao Su, Xiang Long, Chengming Dai, Bihui Cao, Linjiang Han, Yuliang Zhou, Yufeng Deng, Changjiang Yu, Tucheng Sun, Zerui Chen, Ping Zhu, Shuoji Zhu, Yeneng Dai, Qi Zhao, Nanbo Liu.

Ischemic heart disease remains a leading cause of global mortality, primarily driven by myocardial infarction and subsequent ischemia-reperfusion injury (MI/RI) following coronary artery occlusion. This highlights a critical unmet clinical need for integrated strategies that enable both timely intervention during the acute phase and precise postinjury assessment of myocardial damage. Here, we report a theranostic platform based on a dual-modality near-infrared II fluorescence and photoacoustic imaging probe targeting the angiotensin II type 1 receptor (AT1R). The system is coloaded with losartan and exosomes derived from induced pluripotent stem cell-derived cardiomyocytes (iCMs), enabling noninvasive, high-resolution visualization and evaluation of myocardial injury. Under imaging guidance, this platform allows spatially precise delivery of therapeutics, thereby integrating the antifibrotic and anti-inflammatory effects of AT1R blockade with the regenerative paracrine signaling mediated by iCM-derived exosomes. The synergistic therapeutic efficacy of this system was systematically validated in established mouse and rat models of MI/RI, demonstrating enhanced angiogenesis, attenuation of fibrosis, and improved cardiac functional recovery. Collectively, this study establishes a multifunctional platform that integrates diagnosis and therapy, providing a promising strategy for the precise management of MI/RI.

DOI: https://doi.org/10.1126/sciadv.aef1504

Cardiovasc Diagn Ther. 2026 Aug 31. 16(4): 62

Biomarkers in plasma and extracellular vesicles for early detection of asymptomatic ischemic heart disease: a retrospective case-control study.

Chris Lenselink, Daan Ties, Geert H D Voordes, Adriaan A Voors, Dominique P V de Kleijn, Rozemarijn Vliegenthart, Pim van der Harst, Erik Lipsic.

Background: Asymptomatic ischemic heart disease (aIHD) often precedes acute coronary syndrome (ACS). Early detection of aIHD with evidence-based treatment may reduce the risk of ACS and sudden cardiac death. Current risk prediction modalities may not fully capture at-risk patients. We aimed to explore whether plasma and extracellular vesicle (EV) proteins could help predict aIHD in at-risk individuals.
Methods: We performed a pilot case-control study in asymptomatic individuals with a coronary artery calcium (CAC) score of >300 who underwent stress-perfusion cardiac magnetic resonance (CMR) imaging in three Dutch hospitals between May 2019 and September 2020. In total, 44 participants demonstrated the presence of aIHD (myocardial ischemia or infarction), and 43 did not. Plasma and EV protein concentrations were measured using the Olink Cardiovascular III panel (92 proteins). Differential expression was used to identify potential biomarkers with correction for multiple testing using the Benjamini-Hochberg method. Forward and backward logistic regression analysis was performed to identify independent clinical and proteomic predictors for aIHD. The trial was registered at ClinicalTrials.gov (NCT04680338; date registered 2020-12-22).
Results: Baseline patient characteristics between patients with and without aIHD were similar; only hypertension was more prevalent in patients with aIHD (P=0.02). After Benjamini-Hochberg correction for multiple testing, no proteins were differentially expressed in groups with and without ischemia. However, in logistic regression models, higher plasma aminopeptidase-N [AP-N, odds ratio (OR) 8.74, 1.12-68.37, P=0.04], retinoic acid receptor responder protein 2 (RARRES2, OR 12.64, 1.88-85.15, P=0.009), and chitinase-3-like protein (CHI3L1, OR 0.54, 0.30-0.96, P=0.04) were independently associated with aIHD. After determining threshold values with the Youden index, the sensitivity for aIHD was 0.84 for AP-N, 0.93 for RARRES2, and 0.93 for CHI3L1. Positive predictive value was 0.62, 0.62, and 0.52, respectively. In an EV model, AP-N was able to predict the presence of aIHD (OR 7.24, 1.34-39.14, P=0.02). In a combined plasma and EV model, RARRES2 in plasma (OR 12.77,1.76-92.73, P=0.01) and AP-N in EVs (OR 13.27, 2.04-86.37, P=0.007) remained independently associated with aIHD. Established clinical risk scores [Systematic Coronary Risk Evaluation (SCORE), Framingham Heart Study (FHS)] did not discriminate aIHD (area under the curve <0.60).
Conclusions: In this exploratory study, selected protein biomarkers showed potential to help identify aIHD in asymptomatic individuals with a high CAC score. These preliminary findings support further validation of AP-N and RARRES2 as gatekeepers for non-invasive risk stratification.

Keywords: Biomarkers; asymptomatic ischemic heart disease (aIHD); cardiac magnetic resonance imaging (CMR); early diagnosis; myocardial ischemia

DOI: https://doi.org/10.21037/cdt-2025-1-678