Research Projects

Cardiovascular diseases (CVDs) are a major cause of death worldwide, particularly in India. Vascular smooth muscle cells (VSMC) in blood vessels play a crucial role in CVDs. When stimulated by injury and growth factors like Angiotensin II (AngII), VSMC de-differentiate through phenotypic switching, leading to vascular remodeling and dysfunction. Diabetic conditions also promote VSMC phenotypic switching and accelerate CVD. The molecular mechanisms involved in VSMC phenotypic switching under diabetes and AngII stimulation are unknown. This proposal aims to investigate the diabetes-induced epigenetic alterations of genes associated with phenotypic switching using integrative genome-wide approaches. VSMC will be isolated from diabetic mice treated with or without AngII type 1 receptor blocker losartan versus control mice. The study will validate candidate targets in VSMC isolated from diabetic mice and patients using CRISPR/Cas9 genome editing. The proposed studies will uncover novel epigenetic alterations caused by AngII-dependent and -independent processes in diabetic conditions and their functional relevance to VSMC phenotypic switching. The study will also identify unique crosstalk among the various epigenetic layers, which leads to CVD in diabetes even after glycemic control. This study is significant and innovative, providing new insights into the epigenetic mechanisms involved in VSMC phenotypic switching in diabetes. These studies may identify new targets and therapeutics to ameliorate or reverse diabetes-related CVD.