Revisiting the multiple roles of T-cadherin and adiponectin in cardiovascular disease: from receptor function to exosome-mediated therapeutic potential.

Cardiovascular disease, particularly ischemic heart disease, remains a leading cause of death worldwide. Although advances in pharmacological and device-based therapies have improved clinical outcomes, effective strategies for myocardial repair and regeneration remain limited. T-cadherin, a glycosylphosphatidylinositol-anchored atypical cadherin, has recently been identified as a functional receptor for both low-density lipoprotein cholesterol and adiponectin, a cardioprotective adipokine. Notably, the interaction between T-cadherin and adiponectin has emerged as a key regulator of exosome biogenesis and paracrine signaling within cardiovascular tissues. Exosomes are nanosized extracellular vesicles that carry protective molecular cargo, including microRNAs and proteins, and contribute to anti-inflammatory, antifibrotic, and angiogenic effects in the ischemic myocardium. However, their clinical translation is challenged by factors such as variability in yield, heterogeneity of exosome populations, and inefficient tissue targeting. Enhancing endogenous exosome production through the T-cadherin-adiponectin pathway may therefore offer a novel cell-free therapeutic strategy. This review explores the biological roles of T-cadherin and adiponectin in cardiovascular diseases, their regulatory influence on exosome formation, and the future potential of leveraging this axis for myocardial repair and regeneration.