Abstract P3125: Cldn11 Is A Candidate For Vascular Smooth Muscle Cell Plasticity Regulator In Atherosclerosis Pathology

Claudin-11(CLDN11) is a component of tight junction, and important for normal CNS functions. The function of CLDN11 is well elucidated in oligodendrocytes and CNS system, but its expression pattern according to human vascular bed such as intracranial and extracranial, role in the vascular smooth muscles (vSMCs) plasticity and atherosclerosis is still unknown. Human left anterior descending coronary artery (LAD) and middle cerebral artery (MCA) vascular smooth muscle layer was dissected from the dead body. CLDN11 expression is identified in LAD and MCA vascular smooth muscle cell layer, and the CLDN11 expression is higher in MCA than in LAD (p<0.01). Interestingly, the CLDN11 expression is decreased in vSMCs around the atherosclerotic lesions compare to non-atheromatous lesions by immunohistochemistry. To determine the functional role of CLDN11 in vSMCs, microarray analysis was performed following siCLDN11 knockdown. Compared to normal HASMC (human aortic vascular smooth muscle cells), siCLDN11-HASMC was showed increased gene expression such as RSPO3, CXCL8, EGR3, CYP1B1, TNFAIP2, PTGS2, HEY1, BMPER and these set was related to cell migration, proliferation and angiogenesis. CLDN11 knockdown vSMCs showed increased the cell migration of HASMC measured by wound healing, tube formation, and cell cycle assay, and reduced cas-3 cleavage. Finally, CLDN11 expression was inversely correlated with the progression of coronary atherosclerosis and the sudden cardiac death with complicated coronary atherosclerosis. This study shows that CLDN11 play a role in the initiation and propagation of atherosclerosis by regulating the plasticity of vSMCs, suggesting the possibility of biological marker for atherosclerosis in clinical diagnosis (This work was supported by NRF-2019R1A2C1089108, NRF-2019M3E5D1A02068082, COMPA-2022C100, and BK21 Program, Center for Glocal Future Biomedical Scientists at Chonnam National University).