MicroRNA expression with “aging” in human aortic endothelial cells

Abstract

Vascular endothelial cell “aging” is associated with development of a senescent phenotype featuring oxidative stress, inflammation, increased extracellular matrix (ECM) and collagen deposition, and impaired angiogenesis. We hypothesized changes in micro‐RNAs (miR) known to modulate expression of proteins associated with these altered functions in human aortic endothelial cells (HAEC) with aging. HAEC aged to replicative senescence (45±1 population doublings (PDLs)) had greater % of cells stained for senescence‐associated β‐galactosidase (60±7% vs. 7±1%), expression of collagen I (+5.0±0.04‐fold, P<0.05) and vascular cell adhesion molecule‐1 (VCAM‐1, +3.6±0.8‐fold, P<0.05) protein (western blotting), and superoxide production (+2.7±0.3‐fold, P<0.001) (electron paramagnetic resonance) vs. early passage HAEC (28.0±0.4 PDLs). Consistent with these changes, senescent HAEC had lower expression of: collagen‐repressing miR‐29 (0.2±0.1 vs. 1.0±0.3 AU, P<0.05); miR‐21 (0.4±0.1 vs. 1.0±0.2 AU, P<0.05) and miR‐214 (0.3±0.1 vs.1.0±0.3 AU, P<0.05), two miRs that target PTEN, a tumor suppressor and cell cycle regulator; and miR‐126 (0.5±0.2 vs. 1.0±0.1 AU, P<0.05), which induces angiogenesis and down‐regulates VCAM‐1. In contrast, redox‐sensitive miR‐125 was greater in senescent HAEC (2.2±0.4 vs. 1.0±0.3 AU, P<0.05). Changes in miR may play an important role in development of a senescent phenotype in vascular endothelial cells and contribute to arterial endothelial dysfunction and increased risk of cardiovascular diseases with aging.NIH AG013038, AG029337, HL007822, Swedish Research Council