Dr. Sadhan Chandra Das, CSIR-CDRI, Lucknow
Diabetes and metabolic disorders significantly advance the development of cardiovascular diseases such as atherosclerosis and hypertension. Recent evidence shows that epigenetic factors and noncoding RNAs triggered by changing lifestyles and environment, may be new players in these pathologies. Angiotensin II (AngII), a peptide hormone, promotes hypertension and atherosclerosis by activating growth-promoting and pro-inflammatory gene expression in vascular smooth muscle cells. However, the genome-wide changes in distal regulatory elements (enhancers) triggered by AngII were previously unknown. I have delineated the AngII-induced signals that integrate enhancers/super-enhancers and long noncoding RNA (lncRNAs) to promote the expression of genes involved in vascular smooth muscle cell dysfunction. Moreover, I have demonstrated that inhibition of super enhancer-binding protein BRD4 attenuates AngIIinduced enhancers/super-enhancers and inflammatory genes in vascular smooth muscle cells and ameliorates AngII-induced hypertension, medial hypertrophy, and inflammation in mice that could lead to the development of novel therapeutics for cardiovascular diseases in diabetes. In addition, I will discuss the role of AngII-induced phenotypic switching in vascular pathologies using single-cell approaches.
Meeting ID: 947 4448 5153