VASCULAR SMOOTH MUSCLE CELL PHENOTYPIC DIFFERENTIATION AND METABOLIC DYSFUNCTION IN THORACIC AORTA ATHEROSCLEROSIS

BackgroundChanges in vascular smooth muscle cells (vSMC) have proven to be a contributing factor the development and progression of atherosclerosis. Following arterial injury, vSMCs can undergo differentiation acquire phenotypes resembling foam cells, mesenchymal stem osteochondrogenic which all aid intimal plaque formation promote stenosis. Dynamin-related protein 1 (Drp1) is cytosolic GTPase that mediates mitochondrial fission. Increased fission affiliated with SMC proliferation migration, thus increasing neointimal hyperplasia, forming an anatomical basis for atherosclerosis development. We hypothesize metabolic (dys)function critically involved plasticity. Alterations morphology energy production may atherogenic phenotypic switching remain studied.Methods ResultsMitochondrial dynamics cellular metabolism were assessed contractile, synthetic, lipid-loaded, adipogenic, osteogenic SMCs. To study role Drp1 atherosclerosis, both male female murine models developed by AAV-mediated proprotein convertase subtilisin/kexin type 9 (PCSK9) overexpression high-fat diet feeding. Via degradation LDL receptors, PCSK9 upregulation resulted hyperlipidemia Smooth cell-specific knockdown mice littermate controls subjected AAV8-PCSK9 injection feeding; was evaluated using echocardiography histological analyses. Sex-specific research questions generated based on observations from factorial statistical analysis.ConclusionUnderstanding alterations different could fundamental finding therapeutic target mitigate pathologic identified previously undescribed Drp1-mediated changes vSMC differentiation. Additionally, we initated our investigation analyzing studied. Changes Methods analysis. Mitochondrial ConclusionUnderstanding Understanding