Sestrin2 at the crossroads of cardiovascular disease and diabetes: A comprehensive review

Abstract

Cardiovascular diseases and Diabetes Mellitus are major global burdens, ranked at the highest in mortality rates; hence, there is an immediate need for new therapeutic targets. This review focuses on Sestrins and, in particular, SESN2, since it has a dual role in modulating oxidative stress and regulating cardiovascular health. Sestrins are stress-responsive proteins of great importance in cellular defense from oxidative damage, which is a key contributor to cardiovascular pathologies such as heart failure, atherosclerosis, and myocardial infarction. The last advances have shown that Sestrins participate in defense mechanisms against oxidative insults and mismanagement of metabolic and immune responses. These features place Sestrins among the valuable biomarkers and possible therapeutic targets in cardiovascular medicine. We synthesize current research relating molecular mechanisms to clinical application with a focus on the potential of Sestrins to shift treatment paradigms. In this article, we capture the translation of Sestrins for clinical use and their role in the management and disease prevention. We also outline the need for future research for the validation of this therapeutic efficacy of Sestrins across diverse populations and further characterization of their interactions within the complex network of cardiovascular pathology. Such research may, therefore, unlock novel treatment options and strategies toward managing and preventing CVD and DM in line with the urgent need for more effective intervention in the face of the rising prevalence of cardiovascular disease globally.