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Age‐related remodeling of small arteries is accompanied by increased sphingomyelinase activity and accumulation of long‐chain ceramides
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Age‐related remodeling of small arteries is accompanied by increased sphingomyelinase activity and accumulation of long‐chain ceramides
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Journal Article
Age‐related remodeling of small arteries is accompanied by increased sphingomyelinase activity and accumulation of long‐chain ceramides
2014
Overview
The structure and function of large arteries alters with age leading to increased risk of cardiovascular disease. Age‐related large artery remodeling and arteriosclerosis is associated with increased collagen deposition, inflammation, and endothelial dysfunction. Bioactive sphingolipids are known to regulate these processes, and are also involved in aging and cellular senescence. However, less is known about age‐associated alterations in small artery morphology and function or whether changes in arterial sphingolipids occur in aging. We show that mesenteric small arteries from old sheep have increased lumen diameter and media thickness without a change in media to lumen ratio, indicative of outward hypertrophic remodeling. This remodeling occurred without overt changes in blood pressure or pulse pressure indicating it was a consequence of aging per se. There was no age‐associated change in mechanical properties of the arteries despite an increase in total collagen content and deposition of collagen in a thickened intima layer in arteries from old animals. Analysis of the sphingolipid profile showed an increase in long‐chain ceramide (C14–C20), but no change in the levels of sphingosine or sphingosine‐1‐phosphate in arteries from old compared to young animals. This was accompanied by a parallel increase in acid and neutral sphingomyelinase activity in old arteries compared to young. This study demonstrates remodeling of small arteries during aging that is accompanied by accumulation of long‐chain ceramides. This suggests that sphingolipids may be important mediators of vascular aging. e12015 In this study, we have investigated remodeling of small arteries in a large animal model of aging, the sheep. We show that there is age‐related formation of neointima and increased collagen deposition that is accompanied by changes in sphingolipid metabolism resulting in ceramide accumulation in the tissues. These are the first data implicating sphingolipids as important mediators of vascular aging in small arteries. Given that aging is a major risk factor for cardiovascular disease, our study opens a new area for further research into the mechanisms that underlie vascular remodeling in aging.
Publisher
John Wiley & Sons, Inc,Wiley Periodicals, Inc
Subject
