Restoring Elastin With MicroRNA-29

Abstract

Elastin (Eln) is a highly distensible protein that enables tissues such as lung, skin, and large arteries to expand and return to their original shape.1 Tropoelastin is encoded by a single copy gene that is highly expressed in utero and then strongly downregulated after birth.2,3 Only low maintenance levels of tropoelastin mRNA are found in most elastic tissues in adults.3,4 Repair of severe injuries, such as third-degree burns, produces tissue that is often heavily scarred and severely limited in flexibility, range of motion, and tissue function.5 Similar scarring is seen after prolonged cancer radiation therapy, in sun-damaged skin,6 and in systemic sclerosis.7,8 In the vasculature, Eln haploinsufficient phenotypes include narrowing (stenosis) of the ascending aorta in the perinatal period and hypertension later in life. Overdistention injury of arteries after balloon catheter-based therapies activates repair responses in the adventitia that closely resemble skin wound contractures and can drive lumen narrowing in restenosis.9 These aberrant conditions have in common the production of a collagen-rich extracellular matrix (ECM) that is deficient in elastic fibers. A major cause of the deficiency in elastic fiber production is the failure to upregulate tropoelastin gene expression in postnatal tissues subject to the injuries described above. An article by Zhang et al in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology describes a novel approach to increase Eln production that may change clinical outcomes in conditions such as those described above.10 See accompanying article on page 756 The elastic fiber is built up by a stepwise addition of tropoelastin monomers on a microfibrillar scaffold (Figure). The core of a microfibril is composed of the glycoprotein fibrillin.11 Fibrillin is deposited in the extracellular space and once there interacts with a group of microfibril-associated proteins, …