The myriad essential roles of microRNAs in cardiovascular homeostasis and disease.

According to the World Health Organization, cardiovascular disease accounts for approximately 30% of all deaths in the United States, and is the worldwide leading cause of morbidity and mortality. Over the last several years, microRNAs have emerged as critical regulators of physiological homeostasis in multiple organ systems, including the cardiovascular system. The focus of this review is to provide an overview of the current state of knowledge of the molecular mechanisms contributing to the multiple causes of cardiovascular disease with respect to regulation by microRNAs. A major challenge in understanding the roles of microRNAs in the pathophysiology of cardiovascular disease is that cardiovascular disease may arise from perturbations in intracellular signaling in multiple cell types including vascular smooth muscle and endothelial cells, cardiac myocytes and fibroblasts, as well as hepatocytes, pancreatic β-cells, and others. Additionally, perturbations in intracellular signaling cascades may also have profound effects on heterocellular communication via secreted cytokines and growth factors. There has been much progress in recent years to identify the microRNAs that are both dysregulated under pathological conditions, as well as the signaling pathway(s) regulated by an individual microRNA. The goal of this review is to summarize what is currently known about the mechanisms whereby microRNAs maintain cardiovascular homeostasis and to attempt to identify some key unresolved questions that require further study.