bims-evecad 2025-12-07 papers

Issue of 2025–12–07
four papers selected by
Cliff Dominy

Basic Clin Pharmacol Toxicol. 2025 Dec;137(6): e70151

Exosomes in Cardiovascular Disease: Emerging Roles, Therapeutic Potential and Translational Challenges.

Adnan Taan Al Khafaji, Ali Mohammed Barakat, Akram Jooda Al Zaidy, Ali Adnan Taan, Raed Fanoukh Aboqader Al-Aouadi.

Cardiovascular diseases (CVDs) remain a leading global cause of mortality, necessitating novel therapeutic strategies to address myocardial injury, adverse remodelling and impaired cardiomyocyte regeneration. Exosomes, nanoscale extracellular vesicles secreted by nearly all cell types, have emerged as pivotal mediators of intercellular communication, influencing cardiac physiology and pathology through their cargo of nucleic acids, proteins and lipids. These vesicles participate actively in processes such as cytoprotection, angiogenesis, apoptosis regulation and immune modulation, which are critical for cardiac repair and regeneration. Recent preclinical and clinical studies highlight the promising regenerative capabilities of exosomes, especially those derived from stem cells and immune cells, positioning them as innovative therapeutic tools and diagnostic biomarkers in CVD management. Despite their potential advantages over traditional cell therapies, including lower immunogenicity and enhanced targeting, several hurdles remain before exosomes can be routinely applied in clinical practice. Challenges include the lack of standardized isolation and characterization protocols, heterogeneity of exosome populations, inefficient cargo loading methods, off-target biodistribution and safety concerns related to immune response and infectious risk. Ongoing research aims to overcome these obstacles to realize exosomes' full potential in cardiovascular regenerative medicine, with diagnostic applications currently representing a nearer-term goal.

Keywords: cardiac regeneration; cardiovascular diseases; exosomes; intercellular communication; therapeutic delivery

DOI: https://doi.org/10.1111/bcpt.70151

Am J Physiol Heart Circ Physiol. 2025 Dec 01.

Dynamics and Biodistribution of Cardiomyocyte-Derived Small Extracellular Vesicles Following Myocardial Infarction: Sex Differences.

Xinjie Wang, Xiao Du, Zhishi Chen, Wei Yu, Zhongjing Wang, Yanping Chen, Daniel Y Chang, Garrett Jensen, Weijia Luo, Jiang Chang.

Small extracellular vesicles (EVs) have become essential mediators of intercellular and inter-organ communication in vivo, with significant therapeutic potential and prognostic value in cardiovascular diseases. Despite extensive research on exosomal cargoes and their biological effects, the in vivo dynamics and systemic distribution of cardiac-derived small EVs under pathological conditions remain poorly understood. This study used cardiac exosome-tracking mice to profile the distribution and production of cardiomyocyte-derived small EVs following myocardial infarction (MI). We observed distinct temporal dynamics in cardiac exosome uptake between males and females. In the heart, uptake increased markedly during the acute injury phase and declined during the healing phase in males, while it gradually declined in females, with both sexes showing preferential uptake by endothelial cells and leukocytes. The distribution of cardiac-derived small EVs in peripheral organs gradually decreased over time in male mice but followed different patterns in females. Females exhibited higher circulating levels of cardiac-derived small EVs and a more dynamic uptake into peripheral organs than males. Meanwhile, cardiac exosome biogenesis tended to increase on day 3 but significantly decreased by day 14 in male MI hearts, while it increased in females as MI progressed. These findings provide the first comprehensive in vivo spatial and temporal map of endogenous cardiac exosome dynamics after MI and its sexual dimorphism, laying a crucial foundation for future mechanistic studies.

Keywords: Cellular communication; Genetic mouse model; Myocardial infarction; Sex difference; Small extracellular vesicles

DOI: https://doi.org/10.1152/ajpheart.00835.2025

Curr Probl Cardiol. 2025 Nov 28. pii: S0146-2806(25)00230-0. [Epub ahead of print]51(3): 103211

Progress on application of exosomes on cardiovascular disease: A ten-year retrospective analysis.

Zichun Tang, Shuang Feng, Zongwei Xiao.

BACKGROUND: Exosomes, nanoscale extracellular vesicles (30-150 nm) carrying bioactive molecules (e.g., miRNAs, proteins), have emerged as pivotal mediators in cardiovascular diseases (CVDs), offering potential as diagnostic biomarkers and therapeutic vectors. Despite growing interest, a comprehensive analysis of global research trends, hotspots, and translational gaps in exosome applications for CVDs remains limited.
METHODS: We conducted a ten-year (2016-2025) bibliometric analysis of 2617 publications from the Web of Science Core Collection, employing integrative tools (LDGAS and KMVS) to map research distribution, collaborations, and citation trends. Data was analyzed for contributions by country, institution, journal, and author, with a focus on mechanistic insights, clinical applications, and technological innovations.
RESULTS: Global publications surged post-2016, with China leading in output (50 % of top institutions) and the USA/Europe dominating citation impact (e.g., Harvard Medical School: 7.83 citations/paper). Three key themes emerged: exosomal regulation of oxidative stress, inflammation, and angiogenesis; engineered exosomes (e.g., inflammation-targeting macrophage exosomes and stem cell-derived exosomes; circulating miRNAs (e.g., miR-21-5p in heart failure). Challenges include heterogeneous exosome isolation methods (<5 % studies reach preclinical trials) and imbalanced collaborations (China-USA partnerships dominated, 83 %).
CONCLUSIONS: Exosome research in CVDs demonstrates transformative potential but requires standardized protocols, diversified clinical trials, and strengthened global partnerships. Prioritizing AI-driven biomarker discovery and interdisciplinary synergy will accelerate clinical translation.

Keywords: Biomarker; Cardiovascular disease; Exosomes; Extracellular vesicle; Retrospective analysis

DOI: https://doi.org/10.1016/j.cpcardiol.2025.103211

Mol Neurobiol. 2025 Dec 04. 63(1): 250

Extracellular Vesicles: a Promising Therapy for Treatment of Central Nervous System Ischemia Reperfusion Injury.

Limei Wang, Xinzhu Zhu, Peiwen Jia, Hong Ma, Fengshou Chen.

Central nervous system ischemia-reperfusion injury, including cerebral ischemia reperfusion injury (CIRI) and spinal cord ischemia reperfusion injury (SCIRI), poses significant challenges in neurology. This condition is characterized by severe tissue damage following the restoration of blood flow after an ischemic event. Current therapeutic strategies primarily focus on re-establishing perfusion but often fail to address the secondary injuries induced by reperfusion, underscoring the need for innovative treatment. Extracellular vesicles (EVs) facilitate intercellular communication by transferring proteins, lipids, and nucleic acids, thereby influencing cellular pathways. This review examines the potential of EVs as a promising therapeutic strategy for central nervous system I/R injury. Growing evidence suggests that EVs can mitigate pathological mechanisms in both CIRI and SCIRI. Preclinical studies demonstrate that EVs derived from stem cells, astrocytes, and immune cells have shown potential in reducing damage and promoting recovery. Despite encouraging preclinical outcomes, the clinical translation of EV-based therapies faces several challenges, including standardization of EV production, optimization of delivery methods, and comprehensive evaluation of their safety and efficacy. Future research should prioritize elucidating the molecular mechanisms of EV action, refining production and delivery systems, and conducting clinical trials to assess the long-term therapeutic effects.

Keywords: Central nervous system ischemia–reperfusion injury; Cerebral ischemia reperfusion injury; Extracellular vesicles; Spinal cord ischemia reperfusion injury

DOI: https://doi.org/10.1007/s12035-025-05543-8