bims-evecad 2026-03-01 papers

Issue of 2026–03–01
six papers selected by
Cliff Dominy

J Clin Med. 2026 Feb 15. pii: 1537. [Epub ahead of print]15(4):

Extracellular Vesicles as Biomarkers and Non-Surgical Therapeutics in Cardiovascular Diseases.

Dana A Almazroua, Kelsey C Muir, M Ruhul Abid.

Background: Cardiovascular disease (CVD), including myocardial ischemia, remains the leading cause of mortality. Current therapies for ischemic myocardium rely largely on invasive revascularization strategies, highlighting the need for improved non-invasive diagnostic and therapeutic approaches. Recent studies suggest that extracellular vesicles (EVs) play a critical role in cardiovascular pathophysiology and may offer novel clinical applications. Methods: This review synthesizes current preclinical and clinical literature on EV biology, including their classification, isolation, and characterization methods, and mechanisms of Intercellular communication. Published studies evaluating EVs as biomarkers and non-surgical therapeutics across major cardiovascular conditions were critically analyzed. Results: EVs facilitate intercellular communication by transferring bioactive molecules that influence disease progression and cardiac repair. Accumulating evidence supports their potential utility as biomarkers for disease prediction and severity assessment, as well as cell-free therapeutics in myocardial infarction, cardiomyopathies, atrial fibrillation, and heart failure. However, significant gaps remain, including the lack of validated EV-based biomarkers, inconsistent isolation and characterization methodologies, limited in vivo tracking data, and barriers to clinical translation. Conclusions: EVs represent a promising frontier in non-invasive cardiovascular diagnostics and therapeutics. Addressing current methodological and translational challenges, alongside advances in EV bioengineering, will be essential to realize their full clinical potential in CVD management.

Keywords: bioengineering; extracellular vesicles; myocardial ischemia; stem cells

DOI: https://doi.org/10.3390/jcm15041537

Int Immunopharmacol. 2026 Feb 25. pii: S1567-5769(26)00226-2. [Epub ahead of print]175 116382

Comment on "Exogenous dendritic cell-derived exosomes promote Treg differentiation via IDO1-Kyn-AhR axis and improve cardiac function after myocardial infarction".

Rahul Adnaik, Pratibha Adnaik, Sachin S Mali.

Keywords: Cardiac function; Dendritic cell-derived exosomes; IDO1-Kyn-AhR axis; Myocardial infarction; Regulatory T cells

DOI: https://doi.org/10.1016/j.intimp.2026.116382

Curr Issues Mol Biol. 2026 Feb 03. pii: 174. [Epub ahead of print]48(2):

Plasma-Derived Extracellular Vesicles Inhibit Lipopolysaccharide-Induced Apoptosis and Oxidative Stress in Human AC16 Cardiomyocytes.

Yuli Yang, Tingting Yang, Zhihong Li, Youshuang Zhu.

Sepsis is frequently accompanied by myocardial dysfunction, which significantly worsens clinical outcomes. Lipopolysaccharide (LPS), a key component of Gram-negative bacteria, induces excessive oxidative stress and apoptosis in cardiomyocytes, contributing to sepsis-associated cardiac injury. Plasma-derived extracellular vesicles (EVs) have emerged as important mediators of intercellular communication and cardiovascular protection; however, their role in LPS-induced cardiomyocyte injury remains unclear. In this study, human AC16 cardiomyocytes were exposed to LPS in the presence or absence of plasma-derived EVs. Intracellular reactive oxygen species (ROS) production and apoptosis were assessed by flow cytometry, while apoptosis-related proteins and NF-κB signaling components were analyzed by Western blotting. The involvement of NF-κB signaling was further examined using pharmacological rescue experiments. Our results demonstrate that EV treatment markedly attenuated LPS-induced ROS accumulation and cardiomyocyte apoptosis. These protective effects were associated with reduced phosphorylation of NF-κB p65 and IκBα, as well as inhibition of p65 nuclear translocation. Notably, activation of NF-κB signaling abolished the anti-apoptotic and antioxidative effects of EVs under LPS challenge. Collectively, these findings suggest that plasma-derived EVs mitigate LPS-induced oxidative stress and apoptosis in human cardiomyocytes, potentially through modulation of NF-κB signaling. This study provides molecular insights into the cardioprotective actions of EVs and supports their potential as therapeutic candidates for sepsis-associated cardiovascular dysfunction.

Keywords: NF-κB (p65); lipopolysaccharide; myocardial apoptosis; oxidative stress; plasma-derived extracellular vesicles

DOI: https://doi.org/10.3390/cimb48020174

bioRxiv. 2026 Feb 13. pii: 2026.02.11.705398. [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, Jun Yang, Lauren Hawthorne, Frank Ketchum, Aoife J Lowery, Michael J Kerin, Pinar Zorlutuna.

Cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. While most of these deaths are the result of chronic heart diseases, some CVDs are induced artificially. Doxorubicin (DOX) is a chemotherapeutic that is commonly used to treat breast cancer which is one of the most common types of cancer in the United States. While DOX is an effective anti-cancer agent, over 10% of treated women show signs of acute cardiotoxicity immediately following treatment, and approximately 2% develop severe cardiotoxicity up to 10 years after the end of treatment. Despite this prevalence, the mechanism by which the onset of this cardiotoxicity occurs over time is not well understood. Here, we show that treatment of cardiac cells with DOX changes the cardiac function and the resulting paracrine signaling profile. Subsequent exposure of healthy cells to these altered paracrine agents can recapitulate the effects of direct DOX exposure in 2D and 3D in vitro models. We suggest that this is the result of an altered paracrine miRNA profile and other paracrine factors that propagate the initial disruption caused by direct DOX exposure. 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 tissue-engineered models. Pathway analysis of the most distinguishing 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 the targeting of key clusters of miRNAs to enhance both understanding of and intervention strategies for preventing the onset of DOX cardiotoxicity.

DOI: https://doi.org/10.64898/2026.02.11.705398

FASEB J. 2026 Mar 15. 40(5): e71621

GDF15-Treated iPSC-MSC-Derived Exosomes Alleviate Fibrosis Post-Myocardial Infarction via Repression of the MFAP4/ERK/Drp1 Axis.

Jie Qiu, Qian Han, Ying Shen, Qi Yang, Ziqi Li, Yimei Hong, Junxiu Zhao, Fang Lin, Kexin Ma, Bei Hu, Xiaoting Liang, Yuelin Zhang.

Cardiac fibrosis post-myocardial infarction (MI) induces adverse cardiac remodeling, ultimately resulting in heart failure. Exosomes (EXOs) derived from mesenchymal stem cells (MSCs) have emerged as potent modulators of post-infarction remodeling, capable of limiting fibrotic responses. Our previous study showed that growth differentiation factor 15 as pretreatment promoted the protective effects of MSCs against myocardial fibrosis post-MI via paracrine actions. We investigated whether exosomes derived from GDF15-treated iPSC-MSCs (GDF15-iPSC-MSC-EXOs) could alleviate post-MI fibrosis and further explored the mechanistic pathways underlying their effects. In a mouse model of MI, EXOs released from iPSC-MSCs and GDF15-treated iPSC-MSCs were collected from culture supernatants and subsequently administered intramuscularly around the infarct area. Cardiac fibrosis was assessed by Masson's trichrome staining. A collagen synthesis model in mouse cardiac fibroblasts (mCFs) was established by transforming growth factor-β1 (TGF-β1) treatment in vitro. The mitochondrial morphology of mCFs under TGF-β1 stimulation was evaluated by Mitotracker staining. Delivery of EXOs from GDF15-treated iPSC-MSCs resulted in less fibrotic remodeling and better ventricular function after MI than exosomes from untreated cells. In TGF-β1-stimulated fibroblasts, both exosome types reduced fibrosis markers by preventing mitochondrial fission, with GDF15-iPSC-MSC-EXOs affording stronger protection. These effects were partly attenuated in the presence of the mitochondrial fission activator FCCP. Mechanistically, GDF15, which is rich in GDF15-iPSC-MSC-EXOs, inhibited TGF-β1-induced mCF activation via repression of the MFAP4/ERK/Drp1 pathway through a direct physical interaction with MFAP4. GDF15 conditioning strengthened the capacity of iPSC-MSC-derived exosomes to mitigate cardiac fibrosis following MI via inhibition of mitochondrial fragmentation in CFs by repressing the MFAP4/ERK/Drp1 pathway. GDF15 pretreatment is a novel strategy to enhance the cardioprotection of iPSC-MSC-EXOs against cardiac fibrosis post-MI.

Keywords: cardiac fibrosis; exosomes; growth differentiation factor 15; iPSC‐MSCs; mitochondrial fission

DOI: https://doi.org/10.1096/fj.202504078R

J Inflamm Res. 2026 ;19 546243

Emerging Targets and Treatments for Doxorubicin-Induced Cardiac Inflammation.

Thawatchai Khuanjing, Siriporn C Chattipakorn, Nipon Chattipakorn.

Doxorubicin (DOX) is one of the most effective and widely used anthracycline chemotherapeutic agents, yet its clinical utility is severely limited by cumulative, dose-dependent cardiotoxicity. Currently, clinical management of DOX-induced cardiotoxicity is largely limited to dose adjustment, cardiac monitoring, and nonspecific cardioprotective agents, underscoring the lack of targeted anti-inflammatory strategies in current practice. A growing body of evidence indicates that inflammation is a central driver of DOX-induced cardiotoxicity, synergistically exacerbating oxidative stress, mitochondrial dysfunction, and cardiomyocyte death. These pathological processes not only compromise myocardial contractility, but also accelerate adverse cardiac remodeling, ultimately increasing the risk of heart failure in cancer survivors. Over the past decade, the discovery of non-coding RNAs, including microRNAs (miRNAs) and circular RNAs (circRNAs), and extracellular vesicles such as exosomes has reshaped our understanding of the molecular regulation of cardiac inflammation. These molecules act as crucial modulators of intercellular communication and inflammatory signaling, influencing key pathways such as those involving nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and apoptosis-related cascades. Experimental studies have demonstrated that specific miRNAs and circRNAs suppress the production of inflammatory cytokines, reduce oxidative damage, and enhance survival in DOX-exposed cardiomyocytes and animal models. Similarly, exosome-mediated delivery of protective RNAs or proteins has emerged as a promising approach to mitigate DOX-induced myocardial injury. This review amasses current evidence on the anti-inflammatory functions of miRNAs, circRNAs, and exosomes in DOX-induced cardiac inflammation, highlighting their mechanistic roles, therapeutic potential, and the challenges that must be addressed to move these strategies toward clinical application.

Keywords: cardiotoxicity; circular RNAs; doxorubicin; exosome; inflammation; microRNAs

DOI: https://doi.org/10.2147/JIR.S546243