Introduction
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Emerging evidence shows that exosomes facilitate crucial cell-to-cell communication in the heart, influencing pathological processes such as inflammation, fibrosis, and angiogenesis. This review highlights the biology of exosomes in CVD and explores their potential as biomarkers and therapeutic agents.
Biology of Cardiac Exosomes
Cardiomyocytes, fibroblasts, endothelial cells, and immune cells secrete exosomes containing diverse cargo, including proteins, lipids, and nucleic acids. These exosomes regulate cardiac homeostasis and contribute to disease pathogenesis by transferring molecular signals among cardiac and immune cells [1].
Exosomes in Myocardial Infarction (MI)
MI causes extensive cardiomyocyte death and inflammatory responses. Exosomes contribute to:
- Inflammation modulation: Exosomes from cardiac fibroblasts carry pro-inflammatory miRNAs (e.g., miR-21) exacerbating fibrosis [2].
- Angiogenesis promotion: Endothelial cell-derived exosomes enriched with miR-126 promote new vessel formation, enhancing cardiac repair [3].
- Cardioprotection: Mesenchymal stem cell (MSC)-derived exosomes reduce apoptosis and oxidative stress in ischemic myocardium [4].
Exosome-Based Therapeutics for CVD
Therapeutic applications under investigation include:
- Stem cell-derived exosomes: MSC exosomes loaded with cardioprotective miRNAs reduce infarct size and improve cardiac function in animal models [5].
- Drug delivery: Engineering exosomes to deliver anti-fibrotic or anti-inflammatory drugs directly to damaged myocardium.
- Immunomodulation: Exosomes can be used to modulate immune cell activity post-MI, reducing adverse remodeling.
Diagnostic Potential
Circulating exosome cargo profiles change significantly during CVD progression. For example:
- Elevated exosomal miR-208a correlates with acute MI severity [6].
- Specific protein markers such as cardiac troponin found in exosomes may offer more sensitive detection than free plasma proteins.
Challenges and Future Perspectives
Key hurdles include:
- Isolation of heart-specific exosomes from blood.
- Scaling up production of therapeutic exosomes.
- Understanding long-term safety and biodistribution.
Future work should prioritize engineering exosomes with targeted delivery capabilities and standardizing biomarker validation protocols.
Conclusion
Exosomes represent a promising frontier in cardiovascular medicine, offering new opportunities for diagnosis and therapy. Their unique ability to mediate intercellular communication and deliver bioactive molecules could revolutionize the management of CVD.
📚 References
- Barile L, Vassalli G. Exosomes: Therapy delivery tools and biomarkers of diseases. Pharmacol Ther. 2017;174:63-78. https://doi.org/10.1016/j.pharmthera.2017.02.020
- Bang C, et al. Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J Clin Invest. 2014;124(5):2136-2146. https://doi.org/10.1172/JCI70577
- Jansen F, et al. Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and VEGF signaling. Circ Res. 2013;113(4):e1-e11. https://doi.org/10.1161/CIRCRESAHA.113.301295
- Ibrahim AG-E, et al. Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Reports. 2014;2(5):606-619. https://doi.org/10.1016/j.stemcr.2014.03.003
- Lai RC, et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010;4(3):214-222. https://doi.org/10.1016/j.scr.2009.12.003
- Gidlöf O, et al. Circulating cardio-specific microRNAs as potential biomarkers for acute myocardial infarction. Int J Cardiol. 2011;147(3):326-329. https://doi.org/10.1016/j.ijcard.2010.08.040