bims-evecad 2026-08-30 papers

bims-evecad

Biomed News

on Extracellular vesicles and cardiovascular disease

Issue of 2026–08–30
twelve papers selected by
Cliff Dominy

Doxorubicin-induced Cardiotoxicity is Propagated by Paracrine Signaling through Small Extracellular Vesicles.
Skeletal muscle-heart crosstalk in chronic kidney disease: hierarchical signaling networks underlying myocardial metabolic reprogramming and fibrotic remodeling.
Small extracellular vesicles induced by Angiotensin-(1-7) enhance cardioprotection following myocardial ischemia-reperfusion injury.
Biomaterial-Assisted Stem Cell Therapy and Exosome Delivery in Myocardial Infarction: A Narrative Review.
Molecular Basis of Adipose-Cardiac Crosstalk in Cardiovascular Diseases: From Mechanisms to Therapeutic Opportunities.
Microglia Drive Hypothalamic Inflammation in HFpEF Through Extracellular Vesicles Released From the Heart.
Expression of Concern: Intravenous injection of extracellular vesicles to treat chronic myocardial ischemia.
A Lysis- and Sonication-Based Method for the Quantification of Extracellular Vesicle-Bound Cardiac Troponin T Using a High-Sensitivity Immunoassay.
Nano-enabled natriuretic peptide therapy in post-myocardial infarction heart failure: from functional NP deficiency to dual-axis (cGMP-dependent and -independent) cardioprotection.
Biomarkers of perioperative neurocognitive disorders after cardiac surgery: from mechanistic insights to clinical translation.
Overview of exosomal non-coding RNAs in cardiovascular disease using high throughput sequencing.
Understanding cardiovascular aging as a disorder of mitochondrial network.

Acta Biomater. 2026 Aug 28. pii: S1742-7061(26)00581-7. [Epub ahead of print]

Doxorubicin-induced Cardiotoxicity is Propagated by Paracrine Signaling through Small Extracellular Vesicles.

George Ronan, Lara Ece Celebi, Nicole Kowalczyk, Noor Behnam, Lauren Hawthorne, Jun Yang, Frank Ketchum, Aoife J Lowery, Michael J Kerin, Pinar Zorlutuna.

  Cardiovascular disease (CVD) is the leading cause of death worldwide. Chemotherapy-induced CVD is increasingly recognized as a contributor to long-term morbidity in cancer survivors. Doxorubicin (DOX) is a widely used chemotherapeutic to treat breast cancer, one of the most common cancers in the United States. However, over 10% of treated women experience acute cardiotoxicity immediately following treatment, and approximately 2% develop severe cardiotoxicity up to 10 years after treatment, yet the mechanisms driving this delayed onset remain unclear. Here, we show that DOX treatment of cardiac cells changes their function and paracrine signaling profile. Subsequent exposure of healthy cells to altered extracellular vesicles (EV) recapitulates the effects of direct DOX exposure in 2D/3D in vitro models, suggesting a mechanism for propagating initial injury. Plasma-EV miRNA profiling of blinded patient samples revealed distinct clustering by DOX-cardiotoxicity risk, with high-risk patients exhibiting miRNA signatures similar to those from DOX-treated models. Pathway analysis of miRNAs linked them to cardiac homeostasis and cardiotoxicity-related mechanisms, supporting the potential of plasma-EV miRNAs as noninvasive biomarkers for early risk stratification and personalized cardioprotective interventions in oncological care, and targeting of key miRNA clusters to enhance understanding of and intervention strategies for preventing the onset of DOX cardiotoxicity. STATEMENT OF SIGNIFICANCE: Doxorubicin is an effective chemotherapy drug, but its use is limited by cardiotoxicity that can appear during treatment or years later. The mechanisms driving this delayed injury remain poorly understood. In this study, we show for the first time that small extracellular vesicles released from doxorubicin-treated cardiac cells can propagate doxorubicin-like dysfunction to healthy cardiac cells even in the absence of the drug itself. We further identify broad miRNA cargo changes in these vesicles and show that related vesicle-associated miRNA shifts are also detectable in patient plasma. These findings provide new mechanistic insight into anthracycline cardiotoxicity and highlight extracellular vesicle-associated miRNAs as promising candidates for minimally invasive diagnosis and future therapeutic intervention.

Keywords:  3D bioprinting; bioinformatics; biomaterials; breast cancer; cardiotoxicity; chemotherapy; doxorubicin; extracellular vesicles; tissue engineering

DOI:  https://doi.org/10.1016/j.actbio.2026.08.049
Front Physiol. 2026 ;17 1886745

Skeletal muscle-heart crosstalk in chronic kidney disease: hierarchical signaling networks underlying myocardial metabolic reprogramming and fibrotic remodeling.

Haijing Lu, Boyin Liu, Jiazhou Ji, Lin Shuai, Jingyuan Cao.

  Cardiovascular disease is a major complication of chronic kidney disease (CKD) and often develops alongside skeletal muscle wasting and sarcopenia. These abnormalities are usually studied as separate consequences of CKD, but they may also be linked through shared systemic stressors and inter-organ communication. CKD exposes both skeletal muscle and the myocardium to a persistent uremic milieu characterized by toxin retention, chronic inflammation, oxidative stress, hypoxia, and metabolic disturbance. In this setting, skeletal muscle-heart crosstalk may shift from an adaptive homeostatic program to a maladaptive network that contributes to myocardial metabolic dysfunction and fibrotic remodeling. Under physiological conditions, and especially during exercise, skeletal muscle releases myokines and extracellular vesicles carrying miRNAs, proteins, and other regulatory molecules that support myocardial substrate utilization, mitochondrial function, and repair responses. In CKD, however, altered myokine profiles and dysregulated extracellular vesicle cargoes may act on cardiomyocytes, cardiac fibroblasts, and endothelial cells, promoting impaired metabolic flexibility, extracellular matrix deposition, and progressive cardiac remodeling. The heart may also feed back on skeletal muscle through cardiac-derived endocrine signals and neurohumoral pathways, further reinforcing muscle wasting and systemic dysfunction. In this review, we summarize current evidence on skeletal muscle-heart communication under physiological, exercise-related, and CKD-associated conditions, with emphasis on myokines, extracellular vesicles, and miRNA-mediated signaling. Better definition of this axis may help identify biomarkers and therapeutic targets for CKD-associated sarcopenia and cardiovascular disease.

Keywords:  chronic kidney disease; extracellular vesicles; metabolic reprogramming; myocardial fibrosis; myokines; skeletal muscle–heart crosstalk

DOI:  https://doi.org/10.3389/fphys.2026.1886745
Mol Cell Biochem. 2026 Aug 28.

Small extracellular vesicles induced by Angiotensin-(1-7) enhance cardioprotection following myocardial ischemia-reperfusion injury.

Yalin Wu, Xin Wang, Jianli Zhao, Huiyu Yang, Wenjing Zhang, Zhong Yao, Yao Sun, Yajing Wang, Bin Liang, Zhiming Yang.

  Although Angiotensin-(1-7) [Ang-(1-7)], a non-classical peptide of the renin-angiotensin system (RAS), is widely recognized for alleviating cardiovascular stress through activation of the Mas receptor. we identified a largely Mas receptor-independent pathway that expands its therapeutic potential in cardiac diseases. Our study demonstrated that Ang-(1-7) stimulated cardiomyocytes to release small extracellular vesicles (sEVAng-(1-7)), which exhibit enhanced cardioprotective effects compared with Ang-(1-7) administration alone. In both wild-type C57BL/6J mice and cardiac-specific Mas receptor knockout (cMas-KO) mice subjected to myocardial ischemia/reperfusion injury (MIRI), we found that enriched sEVAng-(1-7) preserved cardiac function by attenuating cardiomyocyte apoptosis and oxidative stress following MIRI. These protective effects remained evident even when Mas receptor signaling was pharmacologically inhibited or genetically ablated. Moreover, in wild-type mice with MIRI, enriched sEVAng-(1-7) provided significantly greater therapeutic efficacy in improving cardiac function than direct administration of Ang-(1-7). In AC16 human cardiomyocytes subjected to hypoxia/reoxygenation (H/R), enriched sEVAng-(1-7) enhanced Akt2 phosphorylation, increased sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity, maintained calcium homeostasis, suppressed endoplasmic reticulum stress signaling (CHOP and p-JNK), and protected AC16 cells against H/R-induced apoptosis. sEVAng-(1-7) also attenuated oxidative stress under these conditions. Importantly, the protective effects of sEVAng-(1-7) remained after Mas receptor knockdown. Separately, Akt2 knockdown (Akt2KD) substantially weakened these benefits. These findings identify sEVAng-(1-7) as an promising therapeutic candidate, offering an effective, largely Mas-independent mechanism to combat MIRI with cardiomyocyte protection.

Keywords:  Akt2; Angiotensin-(1-7); Apoptosis; Endoplasmic reticulum stress; Myocardial ischemia-reperfusion injury; Oxidative stress; Small extracellular vesicles

DOI:  https://doi.org/10.1007/s11010-026-05710-y
Biomimetics (Basel). 2026 Aug 15. pii: 583. [Epub ahead of print]11(8):

Biomaterial-Assisted Stem Cell Therapy and Exosome Delivery in Myocardial Infarction: A Narrative Review.

Amanda-Ioana Răduţă, Andreea-Ramona Treteanu, Octavian Andronic, Ștefan Busnatu, Roxana Nicoleta Silişte, Elena Bălășescu.

  Myocardial infarction remains a leading cause of heart failure because current reperfusion therapies cannot prevent adverse ventricular remodeling or restore lost cardiomyocytes. Regenerative strategies based on stem cells and extracellular vesicles (EVs) have emerged as promising approaches; however, their clinical efficacy is limited by poor retention, rapid clearance, and the hostile post-infarction microenvironment. This narrative review critically examines the role of biomaterial-assisted delivery systems in enhancing stem cell and EV-based cardiac regeneration, with particular emphasis on the distinction between biomimetic and bioactive biomaterials, mechanisms of action, preclinical and clinical evidence, translational barriers, and emerging regenerative technologies. Current evidence demonstrates that injectable hydrogels, extracellular matrix-derived scaffolds, cardiac patches, conductive biomaterials, and multifunctional delivery platforms improve therapeutic retention, prolong paracrine signaling, and actively modulate inflammation, angiogenesis, fibrosis, and extracellular matrix remodeling, resulting in superior functional recovery compared with conventional delivery approaches in preclinical models. Nevertheless, robust clinical evidence remains limited because few biomaterial-assisted strategies have advanced beyond early-phase studies. Future progress will depend on integrating smart biomaterials with engineered extracellular vesicles, gene editing, and personalized regenerative approaches, together with standardized manufacturing, harmonized regulatory frameworks, and adequately powered clinical trials.

Keywords:  biomimetic biomaterials; cardiac regeneration; exosomes; myocardial infarction; stem cell therapy

DOI:  https://doi.org/10.3390/biomimetics11080583
Biomolecules. 2026 Jul 27. pii: 1093. [Epub ahead of print]16(8):

Molecular Basis of Adipose-Cardiac Crosstalk in Cardiovascular Diseases: From Mechanisms to Therapeutic Opportunities.

Siqi Gan, Qixuan Zhang, Chan Zhang, Li Yan, Yue Yin, Heng Ma, Zihui Zhang.

  Cardiovascular diseases remain the leading cause of mortality worldwide and are closely associated with obesity and metabolic dysfunction. Adipose tissue is now recognized as a heterogeneous endocrine and immunometabolic organ that actively communicates with the cardiovascular system through adipokines, inflammatory mediators, metabolites, and extracellular vesicles. Under physiological conditions, adipose-cardiac crosstalk contributes to metabolic and cardiovascular homeostasis, whereas adipose tissue dysfunction promotes inflammation, fibrosis, endothelial injury, and cardiac remodeling. This review summarizes the heterogeneity of adipose depots and their secretomes, discusses the molecular mechanisms underlying adipose-cardiac communication, and highlights their contributions to atherosclerosis, heart failure, hypertension, diabetic cardiomyopathy, and atrial fibrillation. We further discuss emerging biomarkers, therapeutic strategies, and precision medicine approaches targeting the adipose-cardiac axis. Understanding depot-specific signaling networks may facilitate the development of novel diagnostic and therapeutic interventions for cardiometabolic diseases.

Keywords:  adipokines; adipose–cardiac crosstalk; cardiovascular adipose tissue; cardiovascular disease; extracellular vesicles; inflammation; metabolic remodeling

DOI:  https://doi.org/10.3390/biom16081093
Circ Res. 2026 Aug 28. 139(6): e329362

Microglia Drive Hypothalamic Inflammation in HFpEF Through Extracellular Vesicles Released From the Heart.

Hossein Ardehali.



Keywords:  Editorials; central nervous system; heart failure; inflammation

DOI:  https://doi.org/10.1161/CIRCRESAHA.126.329362
PLoS One. 2026 ;21(8): e0357070

Expression of Concern: Intravenous injection of extracellular vesicles to treat chronic myocardial ischemia.

PLOS One Editors

DOI: https://doi.org/10.1371/journal.pone.0357070
Biomedicines. 2026 Jul 23. pii: 1653. [Epub ahead of print]14(8):

A Lysis- and Sonication-Based Method for the Quantification of Extracellular Vesicle-Bound Cardiac Troponin T Using a High-Sensitivity Immunoassay.

Yuetong Leona Ding, Dominika Bernath-Nagy, Chiara Heß, Florian Leuschner, Hugo Albert Katus, Norbert Frey, Jona Benjamin Krohn, Evangelos Giannitsis.

  Background/Objectives: High-sensitivity cardiac troponin (hs-cTn) assays are used in routine diagnostics to detect myocardial injury. However, a fraction of circulating cardiac troponin T (cTnT) enclosed within extracellular vesicles (EVs) goes widely undetected. This study introduces a combined lysis- and sonication-based protocol to release and quantify EV-bound cTnT in a time-efficient manner using a state-of-the-art hs-cTnT immunoassay. Methods: Plasma samples from patients with non-ST-segment elevation myocardial infarction (NSTEMI), unstable angina, pulmonary embolism, decompensated aortic stenosis, atrial fibrillation, myocarditis, and healthy controls were treated with a lysis buffer and subsequently sonicated. Treated and untreated samples were assessed and compared to a conventional EV isolation method. Results: Following combined lysis and sonication, cTnT levels were significantly higher compared to native, unprocessed samples across all cohorts. The median increase post-processing ranged from ~10% in decompensated aortic stenosis to ~34% in young healthy controls. In NSTEMI, the EV-bound cTnT accounted for ~15% of plasma cTnT and remained stable over 72 h. The EV cTnT/plasma cTnT ratios were comparable between the combined lysis and sonication approach and the EV isolation method. Processing time prior to cTnT measurement was reduced from ~2.5 h to ~10 min using the lysis and sonication protocol. Conclusions: Our method allows for the rapid liberation of a previously inaccessible EV-bound fraction of cTnT without the need for time-consuming and resource-intensive EV isolation workflows and is therefore readily implementable alongside standard hs-cTnT testing. The observed EV-cTnT patterns suggest differential compartmentation of cTnT, potentially reflecting the myocardial pathophysiology underlying troponin elevation.

Keywords:  cardiac biomarker; cardiac troponin T; extracellular vesicles; hs-cTnT assay; myocardial injury; myocardial ischemia; sonication; troponin compartmentation

DOI:  https://doi.org/10.3390/biomedicines14081653
Intern Emerg Med. 2026 Aug 28.

Nano-enabled natriuretic peptide therapy in post-myocardial infarction heart failure: from functional NP deficiency to dual-axis (cGMP-dependent and -independent) cardioprotection.

Giulia Cevoli, Ivan Isaia, Reza Parvan, Horng H Chen, Lorenzo Malatino, John C Burnett, Alessandro Cataliotti.

  Myocardial infarction (MI) remains a major driver of incident heart failure (HF) despite timely reperfusion and guideline-directed medical therapy. Current treatments, largely centered on neurohormonal blockades, attenuate maladaptive pathways but do not restore endogenous cardioprotective systems. Among these, the natriuretic peptide (NP) network plays a central role in counteracting fibrosis, hypertrophy, sodium retention, and microvascular dysfunction. In advanced HF, impaired prohormone processing, corin dysfunction, and abnormal glycosylation lead to the predominance of biologically less-active NP forms despite elevated circulating levels, resulting in "functional NP deficiency" and insufficient NP-cGMP signaling. From a mechanistic perspective, NP biology can be organized into two complementary axes. The cGMP-dependent axis comprises ANP and BNP signaling via NPR-A and CNP via NPR-B, mediating natriuretic, vasodilatory, and antifibrotic effects. The cGMP-independent axis includes NPR C-mediated signaling and the actions of the ANP mid-sequence fragment proANP31-67, which exerts antifibrotic and cardioprotective effects through a cyclooxygenase-2/prostaglandin E₂/EP4 pathway with minimal systemic hypotension. Nanomedicine offers a strategy to restore these complementary pathways with improved spatiotemporal precision. Lipid and polymeric nanoparticles, biomimetic carriers, and extracellular vesicles can protect NP-derived cargo, prolong bioavailability, and enhance functional cardiac targeting while limiting off-target exposure, although current evidence is largely preclinical. In this review, we examine NP biology in post-ischemic remodeling, the concept of functional NP deficiency, and emerging nano-enabled delivery approaches as potential add-on interventions to contemporary HF therapy. We propose dual-axis "nano-hormonal" strategies integrating cGMP-dependent and cGMP-independent signaling as a testable paradigm for targeted modulation of post-MI remodeling.

Keywords:  CGMP-dependent and cGMP-independent signaling; Functional NP deficiency; Nano-hormonal therapy; Natriuretic peptides; Polymeric nanoparticles; Post-MI HF; ProANP31-67

DOI:  https://doi.org/10.1007/s11739-026-04500-0
Front Neurosci. 2026 ;20 1893171

Biomarkers of perioperative neurocognitive disorders after cardiac surgery: from mechanistic insights to clinical translation.

Xiaojin Li, Rui Yu, Xu Ku, Kaixin Wang, Yawen Peng, Xiangdong Chen.

  Perioperative neurocognitive disorders (PND) after cardiac surgery are common complications that adversely affect postoperative recovery, functional independence, and long-term prognosis. Their pathogenesis is multifactorial, involving cerebral hypoperfusion, microembolism, CPB-related systemic inflammation, BBB disruption, oxidative stress, metabolic dysregulation, neuroimmune imbalance, and host vulnerability. This review summarizes current evidence on major biomarker categories, including neuronal and axonal injury, glial activation, BBB dysfunction, systemic and neuroinflammation, oxidative stress, neurotrophic signaling, metabolic disturbance, extracellular vesicles (EVs), microRNAs, gut-brain axis-related signals, and clinical vulnerability factors. Neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and several inflammatory markers have the most direct clinical evidence, although none has shown sufficient standalone performance for routine use. EVs, microRNAs, metabolomic profiles, pro-resolving mediators, autonomic-neuroimmune indicators, and microbiome-derived signals remain exploratory. However, most candidate biomarkers show limited discriminatory power when used alone, and few have demonstrated incremental value beyond established perioperative risk factors, including age, frailty, preoperative cognitive impairment, hemodynamic instability, and CPB-related variables. Biomarker-informed intervention studies remain predominantly preclinical or hypothesis-generating. Future progress will require standardized outcome definitions, harmonized sampling strategies, multicenter validation, and temporally structured multimodal models tailored to specific clinical purposes, including preoperative risk stratification, early postoperative brain injury monitoring, prognostic assessment, and treatment-response evaluation.

Keywords:  biomarkers; cardiac surgery; neuroinflammation; perioperative neurocognitive disorders; translation

DOI:  https://doi.org/10.3389/fnins.2026.1893171
Eur J Pharmacol. 2025 Nov 15. pii: S0014-2999(25)01031-3. [Epub ahead of print]1007 178277

Overview of exosomal non-coding RNAs in cardiovascular disease using high throughput sequencing.

Mortaza Eivazi, Leila Abkhooie, Kamran Hosseini, Parnia Mobasheran, Tahereh Ebrahimi, Vahideh Tarhriz, Eric Lazartigues.

  Non-coding RNAs including miRNAs, long-ncRNAs, and circular RNAs play crucial roles in cell-to-cell communication and epigenetic regulation. They control gene expression at multiple levels, including transcriptional, post-transcriptional, and translational, thereby influencing associated signaling pathways. Encapsulated within exosomes, micro-vesicles, and apoptotic bodies, ncRNAs can be transported between cells while being protected from harsh environmental conditions. Studies have shown various expression patterns across different cell types and in various physiological and pathological states. However, the precise correlations and extent of their contribution to diseases are still under investigation. Recent studies have reported the involvement of extracellular vesicle-associated ncRNAs in the pathogenesis of cardiovascular diseases, such as hypertension. This involvement has been linked to the regulation of a range of cellular and molecular pathways, including the renin-angiotensin system. Because these exosomes can be stably detected and measured in body fluids, they hold promise as tools for both diagnosis and therapy. This review explores the potential diagnostic utility of cell-derived circulating extracellular vesicle ncRNA-based biomarkers and therapeutic approaches in cardiovascular diseases, utilizing the Next-Generation Sequencing techniques. Additionally, we address significant challenges, recent advancements, and prospects of extracellular vesicle biomarkers, with a focus on their clinical applications in the context of cardiovascular diseases and hypertension.

Keywords:  Biomarker; Epigenetic modulation; Hypertension; Next generation sequencing; Non-coding RNAs

DOI:  https://doi.org/10.1016/j.ejphar.2025.178277
J Cardiovasc Aging. 2026 ;pii: 12. [Epub ahead of print]6(2):

Understanding cardiovascular aging as a disorder of mitochondrial network.

Taslima Akter Shila, Dhrubo Ahmad, Jianli Zhao, Huilan Tan, Bo Wang, John Zhang, Yajing Wang.

  Cardiovascular aging is increasingly recognized as a mitochondrial-initiated systemic network dysfunction, a progressive, integrative failure driven by deteriorating mitochondrial quality and signaling. This review synthesizes emerging evidence linking comprehensive mitochondrial pathology to the erosion of cardiovascular resilience as a network-level dysfunction. Age-dependent remodeling of mitochondrial ultrastructure and component composition disrupts respiratory efficiency, positioning bioenergetic insufficiency as a central determinant of reduced stress tolerance across the cardiovascular system. Concurrently, defects in mitochondrial fission-fusion dynamics and impaired mitophagy propagate dysfunction within the mitochondrial network, amplifying the decline in energetic capacity. Beyond energy failure, the release of mitochondrial DNA, vesicles, and peptides activates innate immune sensors such as the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase-stimulator of interferon genes (cGAS-STING) pathway, initiating chronic sterile inflammation that propagates maladaptive remodeling cascades throughout cardiovascular tissues and distal organs. We challenge the traditional view of mitochondria solely as energy producers, revealing that uncoupled perfusion and energy metabolism, together with nitric oxide imbalance, can serve as early indicators of diastolic dysfunction and ischemic susceptibility. Additionally, we introduce the concept of "mitochondrial age", a composite measure that integrates respiratory function, imaging-based structural indices, and circulating mitochondrial biomarkers to quantify mitochondrial health. This metric may serve as a translational tool for assessing cardiovascular aging through mitochondrial network communication. Finally, we highlight rejuvenation strategies aimed at restoring mitochondrial youthfulness, ranging from behavioral interventions (exercise, time-restricted feeding) to metabolic and molecular therapies targeting nicotinamide adenine dinucleotide (NAD+) metabolism, mitophagy, and endothelial mitochondrial protection. Collectively, this review defines cardiovascular aging as a network-level mitochondrial disorder, offering new conceptual and therapeutic directions for preserving cardiac and vascular function.

Keywords:  Cardiovascular aging; endothelial dysfunction; epidemiology; heart failure with preserved ejection fraction; hypertension; mitochondrial dysfunction; mitophagy

DOI:  https://doi.org/10.20517/jca.2026.07