Interaction Of CircularRNA And MicroRNA-9-5p In The Mediation Of Cardiac Fibrosis In Diabetic Cardiomyopathy
Abstract
Diabetic cardiomyopathy (DCM) is a chronic diabetic complication affecting the heart. It is a significant and independent contributor to heart failure and characterized by cardiac fibrosis and left ventricular hypertrophy. Endothelial cells are the first cells to be damaged by hyperglycemia, leading to epigenetic modifications and subsequent signaling and transcription derangements that lead to endothelial dysfunction and therefore cardiac fibrosis. The role of the two noncoding RNA microRNA-9-5p and circRNA_012164 are investigated using in vivo and in vitro models of hyperglycemia. CircRNA_012164 is upregulated in the hearts of diabetic mice and in cells exposed to high glucose. This results in an inhibition of miR-9 levels, which leads to increased expression of ACTA2, COL1A1, FN1 and FSP1, genes related to cardiac fibrosis. Knockdown of circRNA_012164 recovers miR-9 levels and protects against endothelial dysfunction and fibrosis. Establishment of the circRNA_012164/miR-9 regulatory axis sheds new light on the role of ncRNA in chronic diabetic complications.