Life Sciences & Biotechnology
Title : | Biology of adult aortic valve calcification: A twisted battle between homodimer and heterodimer formation and their therapeutic implications. |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. santanu Chakraborty, Presidency University, Kolkata, West Bengal |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | santanu.zoology@presiuniv.ac.in |
Equipments : | CO2 incubator
Biological safety cabinet for animal cell culture |
Details
Executive Summary : | Cardiovascular diseases (CVDs) pose a significant global threat, affecting over 23.6 million people by 2030. Adult cardiac diseases are often linked to structural and functional insufficiency of adult aortic valves, leading to aortic cusp mineralization, calcification, and dysfunction. Calific aortic valve disease (CAVD) accounts for 5-25% of all CVDs, and research is focused on understanding its induction and progression. surgical interventions for CAVD are limited due to thrombogenicity or degeneration complications, making repair of existing valves more effective than valve replacement. The molecular mechanism of adult aortic valve calcification is unknown. Twist1, a class II basic-helix-loop-helix transcription factor, regulates cell proliferation and migration in various cells. In human diseased calcific aortic valvular cusps, Twist1 protein is detected with unknown functional significance. Class II bHLH proteins can form heterodimers with class I bHLH proteins, termed E proteins, which are widely expressed in many tissues, including heart valves. Id proteins, a class III HLH protein, preferentially dimerize with E proteins and disrupt functional class I/II bHLH heterodimer formation. Twist1 forms Twist1-Twist1 homodimers to form differentiated bone or osteogenic fronts, while heterodimers with E proteins form mesenchymal cells. The dimer status of Twist1 protein in normal adult aortic valvular interstitial cells and during the induction and progression of calcification disease is unknown. This research proposal aims to answer the critical role of Twist1 homodimer versus heterodimer function in adult aortic valve calcification disease, providing novel implications for anti-calcific therapeutics in heart valve clinics. |
Co-PI: | Dr. Arunima sengupta, Jadavpur University, Kolkata, West Bengal-700032 |
Total Budget (INR): | 53,93,360 |
Organizations involved