Abstract
Atherogenic remodeling often occurs at arterial locations with disturbed blood flow (i.e., low or oscillatory) and both aging and western diet (WD) increase the likelihood for pro-atherogenic remodeling. However, it is unknown if old age and/or a WD modify the pro-atherogenic response to disturbed blood flow. We induced disturbed blood flow by partial carotid ligation (PCL) of the left carotid artery in young and old, normal chow (NC) or WD fed male B6D2F1 mice. Three weeks post-PCL, ligated carotid arteries had greater intima media thickness, neointima formation, and macrophage content compared with un-ligated arteries. WD led to greater remodeling and macrophage content in the ligated artery compared with NC mice, but these outcomes were similar between young and old mice. In contrast, nitrotyrosine content, a marker of oxidative stress, did not differ between WD and NC fed mice, but was greater in old compared with young mice in both ligated and un-ligated carotid arteries. In primary vascular smooth muscle cells, aging reduced proliferation, whereas conditioned media from fatty acid treated endothelial cells increased proliferation. Taken together, these findings suggest that the remodeling and pro-inflammatory response to disturbed blood flow is increased by WD, but is not increased by aging.
Highlights
Advancing age and a diet high in saturated fat and/or sugar are risk factors for coronary heart disease and cardiovascular disease mortality[1,2,3]
We find that partial carotid ligation (PCL) resulted in greater oscillatory blood flow, intima-media thickness (IMT), neointima, and macrophage content in the ligated compared with un-ligated carotid arteries
We termed the greater IMT, neointima, and macrophage content as pro-atherogenic remodeling as these are some of the initial features of atherosclerotic development
Summary
Advancing age and a diet high in saturated fat and/or sugar are risk factors for coronary heart disease and cardiovascular disease mortality[1,2,3]. Most studies of aging and atherogenic remodeling examine arterial branch points and curvatures where disturbed blood flow occurs naturally, and these studies are confounded by the cumulative lifelong exposure to this hemodynamic state. To overcome this limitation, we acutely induced disturbed blood flow in vivo by partial carotid ligation (PCL) in mice[13]. We assessed inflammation by the presence of immune cells in the arterial wall and oxidative stress by nitrotyrosine content As these studies focused on pro-atherogenic remodeling, rather than atherosclerotic plaque formation, wildtype mice were studied. We examined the proliferative response of these young and old VSMCs to fatty acid treatment (palmitate) or to treatment with conditioned media from endothelial cells treated with palmitate
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