MircroRNA-19a promotes vascular inflammation and foam cell formation by targeting HBP-1 in atherogenesis

Atherosclerosis, a serious threat to human cardiovascular health, involves inflammation throughout its various stages of development. MicroRNAs play an important regulatory role in macrophages that respond to inflammation, but the underlying mechanisms are largely unknown. In this work, we study the impact of miR-19a in macrophage-derived foam cell formation during atherogenesis. A microarray-based analysis of serums from patients with coronary heart disease in comparison with healthy controls reveals a significant enrichment of miR-19a in the serums of atherosclerosis patients. A higher level of miR-19a is also observed in atherosclerosis-prone ascending aortic wall tissues than in internal mammary artery amongst patients with coronary heart disease. We identify HMG-Box Transcription Factor 1 (HBP-1) as a target gene of miR-19a. HBP1 is repressor of macrophage migration inhibiting factor (MIF) and overexpression of miR-19a increases MIF expression. By administering a miR-19a antagonist to the caudal vein, we found a decrease in atherosclerotic plaques and lipids load in apoE-null mice fed with high-fat diet. These results support inhibition of miR-19a reduces inflammatory reaction and constitutes a potent therapeutic approach against atherosclerosis.