Vascular disorders are mainly caused by atherosclerosis, or a hardening of the arteries, due to a thickening of the artery lining from fatty deposits or plaques. Vascular disease diminishes blood flow in arteries and veins throughout the body causing disorders ranging from leg pain (peripheral artery disease, PAD), to heart disease (coronary artery disease, CAD) and stroke (carotid artery disease). Atherosclerosis is a complex disease involving the interplay of endothelial, inflammatory and vascular smooth muscle cells. The disease is thought to initiate with early disturbances in the endothelium leading to the recruitment of monocytes and T-cells. These inflammatory cells become activated and release a host of cytokines and chemokines which further amplifies the inflammatory process and induces the recruitment of vascular smooth muscle cells (VSMCs) into the developing lesion in the vessel wall. The VSMCs proliferate and undergo a phenotypic change to a fibroblast-like cell which secretes abundant extracellular matrix. As atherosclerotic plaques grow they may rupture, thereby triggering the coagulation cascade and the formation of an occlusive thrombus. If the atherosclerotic artery supplies the brain or heart, the consequences of plaque rupture are frequently catastrophic. Recent studies have revealed a central role for a collection of microRNAs (miRNAs), like miR-126 and -92a in the development of an atherosclerotic plaque.

Endothelial cells line the entire circulatory system from the heart to the smallest capillary. The proper functioning of endothelial cells is fundamental to the stability of the vascular system. The formation of new blood vessels through the process of angiogenesis is critical to vascular development and homeostasis. Aberrant angiogenesis leads to a variety of diseases, such as ischemia and cancer. The endothelial cell-specific miRNA, miR-126, promotes angiogenesis in response to angiogenic growth factors, such as vascular endothelial growth factor (VEGF) or basic fibroblast growth factor, by repressing negative regulators of signal transduction pathways (Wang et al. Dev Cell 2008, Wang et al. Curr Opin Genet Dev. 2009).

miRagen owns exclusive rights to the intellectual property related to miR-126 and -92a in vascular disease and aims to use this knowledge to advance miRNA based therapeutic approaches for vascular diseases.