Research

Life Sciences & Biotechnology

Title :

Long non-coding RNA mediated phenotypic switch in smooth muscle cells: implications for aortic aneurysm

Area of research :

Life Sciences & Biotechnology

Focus area :

Vascular Biology

Principal Investigator :

Dr. kumaraswamy regalla, CSIR- Centre For Cellular And Molecular Biology (CSIR–CCMB), Hyderabad, Telangana

Timeline Start Year :

2024

Timeline End Year :

2027

Contact info :

Details

Executive Summary :

Vascular smooth muscle cells (VSMCs) are crucial for regulating vascular tone, diameter, blood pressure, and blood flow distribution. They retain a high degree of plasticity, allowing remodeling and repair of the vasculature but also driving vascular pathologies. Aortic aneurysm is the second most common disease affecting the aorta after atherosclerosis, characterized by permanent localized dilatation of the aorta. In healthy aorta, smooth muscle cells usually express contractile phonotype, but in response to certain extracellular signals, they undergo profound changes and acquire synthetic phenotype markers. These synthetic SMCs secrete high levels of matrix metalloproteinases, leading to elastin degradation, dilatation, and weakening of aortic walls, leading to aneurysm. There is no approved pharmacological intervention for preventing or treating aneurysm, and there is an urgent need to explore novel therapeutic targets throughout the genome, including non-coding parts. Long non-coding RNAs (lncRNAs) have been shown to regulate critical cellular events in tissue or cell-specific manner, and their deregulation has been linked to pathological changes in several disease conditions. The study proposes studying TUG1 mediated changes in SMCs during AAA development and if targeting TUG1 with antisense Gapmers prevents progression of angiotensin II-induced aortic aneurysm.

Total Budget (INR):

57,81,628

Organizations involved