bims-evecad 2026-05-10 papers

Issue of 2026–05–10
four papers selected by
Cliff Dominy

Drug Deliv Transl Res. 2026 May 05.

Engineered ATP-loaded extracellular vesicles: a dual-functional strategy for improving myocardial infarction therapy.

Farshid Jaberi Ansari, Javad Behroozi, Mohsen Chamanara, Mostafa Shahrezaee, Ali Shakerimoghaddam, Seyed Hossein Mousavi, Amir Amanzadeh, Mohammad Ali Shokrgozar, Hossein Ahmadi Tafti, Mahdi Ghorbani, David W Greening, Reza Heidari.

Myocardial infarction (MI) represents a major component of cardiovascular disease, primarily due to severe energy depletion in ischemic tissue. Extracellular vesicles (EVs) have recently emerged as promising cell-free nanocarriers capable of targeted delivery and intercellular communication. Leveraging these advantages, engineered EVs were investigated in this study as a direct ATP-delivery platform to cardiomyocytes. EVs were functionalized with an anti-myosin antibody to form targeted extracellular vesicles (T-EVs) and subsequently loaded with ATP, generating T-ATP-EVs for selective energy transfer to damaged myocardium. We study viability and apoptosis of ischemia cells by alamar Blue and flowcytometry (annexin-PI) under hypoxic condition in vitro also we use cardiac function, infarct size, and the expression of troponin and α-actin four weeks after MI on MI rat model in vivo for assessment cardiac repair. The results indicate that, compared with no treatment, the use of T-ATP-EVs enhances the viability of hypoxic cells by 46% and reduces apoptosis by 40%. In the animal study, T-ATP-EVs group increase 27% left ventricular ejection fraction (LVEF) also infarct size decrese 28% compared with control group. Additionally, the expression levels of troponin and α-actin increased approximately two-fold when we use T-ATP-EVs in vivo. In this study, T-ATP-EVs were investigated as a strategy to deliver ATP directly to cardiomyocytes and heart tissue . The system described here enhances cardiomyocyte survival and targeting damaged heart tissue which making a significant advancement in the treatment of MI.

Keywords: Deliver energy; Engineered extracellular vehicles; Myocardial infarction; Targeted exreacellular vesicles; treatment of MI

DOI: https://doi.org/10.1007/s13346-026-02143-4

Int J Mol Sci. 2026 Apr 17. pii: 3582. [Epub ahead of print]27(8):

MicroRNAs in Cardiovascular Diseases: Molecular Networks of Cellular Homeostasis, Inflammation, and Pathological Remodeling.

Humberto Vélez-Slimani, Luis A Salazar.

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, underscoring the need to better define the molecular mechanisms that govern cardiovascular homeostasis and disease progression. Among post-transcriptional regulators, microRNAs have emerged as important modulators of endothelial function, vascular smooth muscle cell plasticity, cardiomyocyte integrity, and cardiac fibroblast activity. This narrative review examines how microRNAs orchestrate molecular networks linking cellular homeostasis to inflammation, oxidative stress, mitochondrial dysfunction, apoptosis, fibrosis, angiogenesis, and pathological remodeling across major cardiovascular cell types. It further discusses how these regulatory programs are reflected in specific cardiovascular diseases, including atherosclerosis, hypertension, acute myocardial infarction, heart failure, and arrhythmias. In addition, the review addresses the growing relevance of circulating and extracellular vesicle-associated microRNAs as candidate biomarkers for diagnosis, prognosis, and disease monitoring, as well as their therapeutic potential through mimics, inhibitors, antagomirs, and emerging delivery systems. Finally, current translation barriers are considered, including methodological heterogeneity, limited tissue specificity, delivery challenges, safety concerns, and the need for large-scale clinical validation. Overall, microRNAs are presented as integrative regulators connecting cardiovascular cell biology with disease mechanisms and clinical applications.

Keywords: RNA therapeutics; biomarkers; cardiovascular diseases; extracellular vesicles; fibrosis; inflammation; microRNAs; vascular remodeling

DOI: https://doi.org/10.3390/ijms27083582

Theranostics. 2026 ;16(11): 5804-5815

Human atrial extracellular vesicles suppress NLRP3 inflammasome activation and profibrotic signaling in a patient-specific iPSC model of postoperative atrial fibrillation.

Noreen Ahmed, Bin Ye, Wenbin Liang, Buu-Khanh Lam, Fraser Rubens, Saad Khan, David Courtman, Duncan John Stewart, Darryl Raymond Davis.

Background: Postoperative atrial fibrillation (AF) remains a common and morbid complication of cardiac surgery, driven by inflammation and fibrosis for which targeted therapies are limited. Conventional antiarrhythmic and anticoagulant strategies have little impact on its incidence or recurrence. We previously demonstrated that a single intracardiac injection of extracellular vesicles (EVs) derived from human heart explant-derived cells prevents postoperative AF in preclinical models. The present study aimed to elucidate the mechanisms underlying this protective effect in human cells.
Methods: Induced pluripotent stem cells (iPSCs) were generated from circulating mononuclear cells obtained from cardiac surgery patients at high and low risk for postoperative AF, then differentiated into atrial fibroblasts. These cells were compared with primary human atrial fibroblasts isolated from surgical tissue. Clinical-grade cardiac EVs were manufactured from heart explant-derived cells and characterized for size, surface markers, and microRNA cargo. Both iPSC-derived and primary fibroblasts were exposed to inflammatory (IL-6, TGF-β1, lipopolysaccharide) and fibrotic stimuli, with or without EV treatment. Inflammasome activation and cytokine secretion were assessed by transcript and protein analyses.
Results: iPSC-derived and primary atrial fibroblasts exhibited comparable antigenic and functional profiles and efficiently internalized cardiac EVs. EV treatment markedly suppressed activation of the NLRP3 inflammasome following lipopolysaccharide and nigericin stimulation, resulting in reduced secretion of Caspase-1, IL-1β, and IL-18 and corresponding transcript downregulation. EVs also attenuated IL-6 and TGF-β1 induced fibroblast proliferation, confirming their anti-inflammatory and antifibrotic effects across cell sources and patient risk groups.
Conclusions: This study establishes a patient-specific human cellular model of cardiac fibrosis, a key determinant of postoperative AF, and identifies heart-derived EVs as potent suppressors of inflammasome activation and profibrotic signaling. These findings provide mechanistic insight into the anti-inflammatory and antifibrotic actions of cardiac EVs and support their further development as a cell-free biologic for the prevention of postoperative AF.

Keywords: NLRP3 inflammasome; cardiac fibrosis; extracellular vesicles; induced pluripotent stem cells; postoperative atrial fibrillation

DOI: https://doi.org/10.7150/thno.127433

Front Nutr. 2026 ;13 1790304

The role of microRNAs in cardiovascular disease associated with the consumption of ultra-processed foods: a comprehensive review.

Shengzhou Wen, Dushyantha T Jayaweera, George R Marzouka, Chunming Dong.

Ultra-processed foods (UPFs) now dominate dietary intake in many countries and are consistently associated with higher risks of cardiovascular disease (CVD), including myocardial infarction, stroke, and heart failure. Beyond excess sodium, sugar, and unhealthy fats, UPFs may exert cardiovascular harm through food matrix disruption, processing-generated toxicants, additive exposure, and microbiome perturbation. These upstream insults converge on inflammatory, oxidative, and metabolic signaling pathways that regulate microRNAs (miRNAs), a class of small non-coding RNAs that orchestrate post-transcriptional gene expression across endothelial cells, vascular smooth muscle cells, macrophages, platelets, and metabolic tissues. In this review, we propose a unifying mechanistic framework in which UPF exposure reshapes both intracellular and extracellular vesicle (EV)-associated miRNA networks, thereby linking gut, liver, adipose tissue, and the vascular wall in a feed-forward cardiometabolic signaling loop. We synthesize evidence across epidemiology, experimental models, and human dietary intervention studies, while explicitly distinguishing established, emerging, and speculative mechanisms to avoid over-interpretation. We further discuss translational opportunities, including circulating miRNA/EV-miRNA biomarkers, nutritionally responsive miRNA signatures, and miRNA-targeted therapeutics. Together, this framework positions the UPF-miRNA/EV axis as a plausible molecular bridge between modern dietary exposure and atherosclerotic disease progression, and highlights priority areas for mechanistic validation and clinical translation.

Keywords: atherosclerosis; cardiovascular disease; extracellular vesicles; inflammation; microRNA; nutrigenomics; ultra-processed foods

DOI: https://doi.org/10.3389/fnut.2026.1790304