Abstract 10689: Vascular Senescence and Potential Mechanisms for Increased Susceptibility to Cardiovascular Diseases
Purpose of the study: Aging is a primary non-modifiable risk factor for cardiovascular diseases including atherosclerosis and hypertension. Several studies have shown complex bi-directional shifts in gene expression patterns in senescent endothelial cells. We designed this study to examine the effects of endothelial senescence on key functions and molecules pertinent to initiation and progression of hypertension and myocardial ischemia in greater detail.
Methods: Triplicate cultures from passages 4 (P4) and 12 (P12) human umbilical vein endothelial cells (HUVECs) were analyzed for morphological characteristics and harvested for gene expression (qPCR) and protein content (Western blot) analysis. In parallel experiments, we conducted functional studies including angiogenesis, apoptosis, and NF-κB translocation.
Results: Later passage cells displayed typical enlargement compared to younger counterparts and increased content of oxidatively modified proteins (4-HNE). Senescent cells exhibited significantly higher mRNA for angiotensin II (Ang 2) type 1 (AT1R) and type 2 (AT2R) receptors (AT1R>>AT2R) and dramatically lower expression for ox-LDL receptor LOX-1. These transcriptional changes were mirrored in protein content. Also, in late passage cells NF-κB was found translocated to the nucleus, whereas young cells exhibited exclusively cytoplasmic distribution. On functional level, P12 cells were more susceptible to apoptosis and showed reduced basal and induced angiogenic potential.
Conclusions: Senescent cells display features suggestive of increased susceptibility to more aggressive development of cardiovascular diseases. Increased AT1R expression may lead to proneness to hypertension, whereas elevated susceptibility to apoptosis and diminished LOX-1 expression may be linked to reduced ability for neovascularization and poorer prognosis for myocardial ischemia.
- © 2011 by American Heart Association, Inc.