Noncoding RNAs in Cardiovascular Disease: Pathological Relevance and Emerging Role as Biomarkers and Therapeutics

Abstract

Noncoding RNAs (ncRNA) include a diverse range of functional RNA species - microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) being most studied in pathophysiology. Cardiovascular morbidity is associated with differential expression of myriad miRNAs; miR-21, miR-155, miR-126, miR-146a/b, miR-143/145, miR-223, and miR-221 are the top 9 most reported miRNAs in hypertension and atherosclerotic disease. A single miRNA may have hundreds of messenger RNA targets, which makes a full appreciation of the physiologic ramifications of such broad-ranging effects a challenge. miR-21 is the most prominent ncRNA associated with hypertension and atherosclerotic disease due to its role as a "mechano-miR", responding to arterial shear stresses. "Immuno-miRs", such as miR-155 and miR-223, affect cardiovascular disease (CVD) via regulation of hematopoietic cell differentiation, chemotaxis, and activation in response to many pro-atherogenic stimuli. "Myo-miRs", such as miR-1 and miR-133, affect cardiac muscle plasticity and remodeling in response to mechanical overload. This in-depth review analyzes observational and experimental reports of ncRNAs in CVD, including future applications of ncRNA-based strategies in diagnosis, prediction (e.g., survival and response to small molecule therapy), and biologic therapy.