Abstract 247: Thoracic Aortic Aneurysm and MicroRNA Expression in Bicuspid and Tricuspid Aortic Valve Patients: miR143/145 and miR133a/b Correlate with VSMC Phenotypic Change and CTGF Expression

Abstract

Introduction. Altered microRNA (miRs) expression plays a role in vascular remodeling by regulating smooth muscle cells (VSMC) phenotype and Extracellular matrix (ECM) remodeling. Recently, miR 29 has been linked to thoracic aortic aneurysm (TAA) development by affecting the structural integrity of the vascular wall. TAA occurs in patients with a Bicuspid Aortic Valve (BAV) earlier and more rapidly than in those with a Trileaflet Aortic Valve (TAV). We have recently observed that TAV-TAA aorta is characterized by accumulation of VSMC with synthetic phenotype, ECM disorganization and cellular loss. In contrast BAV-TAA aorta shows accumulation of contractile VSMC. In addition, CTGF, a molecular determinant of VSMC phenotype, is elevated in non-dilated BAV aorta and in both BAV and TAV aneurismal tissues. Hypothesis. We hypothesized that a selective miRs expression may correlate with CTGF levels and VSMC phenotype in the ascending aorta of BAV and TAV patients with and without aneurysm. Methods. A bioinformatics analysis followed by miR143/145, 133a/b and 29a expression tested by quantitative real-time PCR was performed in aortic tissues collected from 16 BAV and TAV patients with and without TAA (n=4 patients/group). Results. We identified a direct correlation between altered miRs expression, CTGF levels and VSMC phenotype in BAV and TAV patients with and without aneurysm: miR-143 was significantly downregulated in TAV-TAA tissues where we observed an accumulation of synthetic VSMC, while was upregulated in BAV non dilated aorta. miR-143/145 expression was upregulated in BAV non dilated and dilated tissues, where we observed an accumulation of contractile VSMC, while was not significantly changed in TAV-TAA tissues. miR-133a/b, recently described as suppressors of CTGF expression, were downregulated in BAV and TAV aneurismal tissues and in BAV non dilated aorta where CTGF levels are strongly upregulated. miR29a, recently reported as a regulator of aortic wall structure, was downregulated in TAV-TAA while no significantly changed in BAV non dilated and dilated tissues. Conclusions. The characterization of miR143/145 and miR133a/b in the tissue of BAV and TAV patients, and their ability to regulate CTGF and VSMC phenotype is a novel risk stratification tool for patients at high risk to develop TAA.