Modulating the MicroRNArchitecture of an Aging Aorta

Abstract

See related article, pages 1115–1119 The 17th century British physician Thomas Sydenham is credited with saying, “A man is as old as his arteries.” Indeed, aging is associated with myriad structural and functional changes in the cardiovascular system.1 In particular, thoracic aortic aneurysms are commonly found in people during the sixth or seventh decade of life and at a frequency of nearly 1 in 16 000 people per year.2 An aneurysm is a balloon-like bulge that is characterized by thinning and weakness of the vascular wall. Enlarged aortic aneurysms are prone to rupture and often result in death. Maintaining the structural integrity of the aorta is critical to its function and is dictated by the biomechanical properties of the 3 different wall layers: the adventitia, media, and intima. Smooth muscle and extracellular matrix within the media are the largest components of the aortic vascular wall. Smooth muscle cell death or dysfunction and perturbations in extracellular matrix deposition are often associated with aging and aneurysms.3 Advances in surgical procedures to treat aortic aneurysms increase life expectancy and reduce morbidity in the young population but are more risky in the elderly because of cardiovascular comorbidity and surgery-related lethality. Therefore, a comprehensive understanding of the changes in molecular signaling events during aortic aging is necessary to develop novel therapeutics for preventing and treating aneurysm formation. Recent studies have pointed to microRNAs (miRNAs) as key regulators of a variety of cardiovascular disorders and biomarkers of disease progression.4,5 miRNAs negatively regulate target mRNAs through Watson-Crick base pairing with complementary sequences in 3′ untranslated regions of …