SORBS2 AS A NOVEL MOLECULAR TARGET IN THE DIAGNOSIS AND TREATMENT OF CARDIOVASCULAR DISEASES

Vollständiger Abstract

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Highlights Sorbs2 is an adaptor and cytoskeletal protein predominantly expressed in the cardiovascular system-specifically in cardiomyocytes, vascular smooth muscle cells, and endothelial cells. It plays a critical role in maintaining myocardial structural integrity, regulating contractility, and facilitating intercellular communication. In addition, Sorbs2 functions as an RNA-binding protein, influencing the stability and translation of mRNAs that encode essential ion channels and junctional proteins. Sorbs2 dysfunction is associated with a wide range of cardiovascular diseases, from cardiomyopathies and arrhythmias to dyslipidemia, hypertension, and diabetic angiopathy. Sorbs2 expression varies depending on the type of pathology and disease stage. For example, in dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, Sorbs2 levels are decreased, correlating with the severity of fibrosis, disruption of intercalated disc structure, and reduced ejection fraction. In pressure overload conditions (aortic constriction model), a compensatory increase in Sorbs2 expression has been observed during myocardial hypertrophy. Conversely, in diabetic vasculopathy, Sorbs2 expression in coronary arteries is reduced, which is linked to impaired BK-channel activity and decreased coronary perfusion. Given its multifunctionality and involvement in key processes underlying cardiovascular pathology, Sorbs2 is emerging as a promising molecular target. Its role in regulating inflammation, ion homeostasis, and myocardial structure suggests that Sorbs2 could serve as both a biomarker and a therapeutic target in cardiovascular diseases. However, further experimental and clinical studies are required to validate its diagnostic value and explore its full therapeutic potential. Abstract Sorbin and SH3 domain-containing protein 2 (Sorbs2) is a multifunctional adaptor protein that plays a key role in regulating cellular architecture, signal transduction, and gene expression in the cardiovascular system. Sorbs2 is highly expressed in cardiomyocytes, vascular smooth muscle cells, and endothelial cells, contributing to both the mechanical stability and electrical excitability of cardiac tissue. Recent studies have demonstrated that Sorbs2 is involved in the pathogenesis of a wide range of cardiovascular diseases, including dyslipidemia, atherosclerosis, hypertension, cardiomyopathies, arrhythmias, atrial fibrillation, congenital heart defects, diabetic vasculopathy, and aortic aneurysms. Beyond its structural role as part of the cytoskeleton, Sorbs2 functions as an RNA-binding protein that regulates the stability and translation of mRNAs encoding proteins of ion channels and intercellular junctions, which are essential for cardiac conduction. Dysregulation of Sorbs2 has been associated with myocardial fibrosis, atrial remodeling, and impaired cardiac contractility. Notably, the data on its role in inflammation are contradictory, highlighting the need for further investigation. This review summarizes current knowledge on the molecular biology of Sorbs2, its regulatory mechanisms, and its pathophysiological relevance in the context of cardiovascular diseases. The potential of Sorbs2 as a diagnostic biomarker and therapeutic target is discussed. A deeper understanding of Sorbs2 may open new avenues for personalized medicine and targeted treatment strategies in cardiovascular pathology.