Life Sciences & Biotechnology
Title : | Mechanistic Role of Pyruvate Dehydrogenase Kinase-4 in smooth Muscle Cell proliferation and Intimal Hyperplasia in The Comorbid Condition of Diabetes. |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Manish Jain, Panjab University, Chandigarh |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | manishjain.cdri@gmail.com |
Details
Executive Summary : | Vascular smooth muscle cell (sMC) proliferation is a common feature of arterial diseases, particularly in arterial restenosis after angioplasty or stent placement. Aerobic glycolysis is a crucial factor in sMC proliferation, and PDK4 is a mitochondrial enzyme that regulates glucose oxidation. This proposal aims to test the hypothesis that PDK4 regulates sMC proliferation and neointimal hyperplasia. The first objective is to determine the role of PDK4 in sMC proliferation, migration, and aerobic glycolysis. The study will use a PDK4-specific inhibitor and siRNA to inhibit PDK4 expression in human and mouse primary sMCs, analyzing functional and metabolic changes. Mitochondrial ROs production, apoptosis, and lactate production will also be determined using commercial kits. The second objective is to define the mechanistic role of PDK4 mediated signaling during sMC proliferation. The study will use co-immunoprecipitation to check the interaction of PDK4 with NF-κB or sTAT3 and CHIP-qPCR to determine whether PDK4 could be a direct transcriptional target of sTAT3. The third objective is to determine the translational potential of targeting PDK4 during intimal hyperplasia in the comorbid condition of diabetes. The study will use wire injury in the carotid artery of C57Bl/6J mice fed a high-fat diet to induce neointimal hyperplasia. The proposed project will provide valuable information about energy metabolism and its functional consequences on sMC function, potentially identifying novel therapeutic targets common to both atherosclerosis and restenosis, which may improve PCI outcomes. |
Co-PI: | Prof. Kanwaljit Chopra, Panjab University, Chandigarh-160014, Dr. Anurag Kuhad, Panjab University, Chandigarh-160014 |
Total Budget (INR): | 27,83,260 |
Organizations involved