Hypertension and Hypercholesterolemia Differentially Affect the Function and Structure of Pig Carotid Artery

Abstract

Abstract-The purpose of this work was to compare the effects of hypertension and hypercholesterolemia on carotid endothelial function, structure, and vasa vasorum density. Seventeen pigs were randomized to a 12-week normal diet without (nϭ5), or with renovascular hypertension (HT; nϭ6), or to a high cholesterol diet (HC; nϭ6). Carotid arteries were studied by organ chambers (endothelial function) and microcomputed tomography (vasa vasorum), and tissue was processed for Sirius red staining and immunoblotting (vascular endothelium growth factor, endostatin, matrix metalloproteinase-9, and matrix metalloproteinase-2). HC and HT showed reduced vasodilation to acetylcholine as compared with controls, but HT also had a lower response to sodium nitroprusside. In addition, HT showed a higher content of organized collagen fibers and increased intima-media thickness. Vasa vasorum density was increased in HC but not in HT. Both HT and HC showed a proangiogenetic biochemical milieu (higher vascular endothelium growth factor, matrix metalloproteinases, and lower endostatin), but this was more pronounced in HC. Both hypertension and hypercholesterolemia induce endothelial dysfunction in the carotid artery. However, hypertension is also associated with greater fibrosis and vascular wall thickening, which might impair endothelium-independent vasorelaxation and vasa vasorum growth. Hypercholesterolemia is, in turn, associated with vasa vasorum neovascularization. These data suggest that carotid atherosclerosis can evolve through different mechanisms in relation to different risk factors. Key Words: carotid artery Ⅲ atherosclerosis Ⅲ hypertension Ⅲ hypercholesterolemia Ⅲ vasa vasorum Ⅲ endothelium S troke is a leading cause of death in Western countries, and in the majority of the cases it is the consequence of an acute complication of an atherosclerotic carotid plaque. Risk factors for carotid atherosclerosis include the traditional cardiovascular risk factors, and, in particular, hypertension plays a major role. 1 Although in the past hypercholesterolemia was not considered a determinant contributor to cerebrovascular disease, 2,3 recent epidemiological studies and clinical trials with lipid-lowering drugs demonstrated a clear relation between serum cholesterol levels and carotid atherosclerosis, as well as with the risk of stroke. 1 Both hypertension and hypercholesterolemia are characterized by similar proatherogenic hallmarks, including endothelial dysfunction, vascular inflammation, and oxidative stress. However, the consequences of the action of these 2 risk factors on the arterial wall might be substantially different. Indeed, different cardiovascular risk factors influence atherosclerosis development favoring preferential plaque characteristics, eventually leading to the formation of morphologically different lesions. 4,5 Experimental analysis of the interaction between hypertension and hypercholesterolemia on the mechanisms of early atherosclerosis indicates that hypertension, per se, induces adaptive remodeling, whe...

Importance of pulsatility in hypertensive carotid artery growth and remodeling

“…Comparing our finding of more thinner (green) collagen fibers at 5 or 8 weeks to the finding by Versari et al [41] of more thicker (red/orange) collagen fibers in porcine carotid arteries at 12 weeks post-surgery in a renovascular model of hypertension suggests that the “maturation” of collagen fibers may take longer than basic geometric changes (cf. [21]).…”

Carotid Proliferative Plaque Formation in a Canine Model of Chronic Hypertension

“…This finding is similar to the results of a prior study using a renovascular hypertensive swine model which showed that carotid IMT became greater at 3 months. 11 These results indicate that 3 to 4 months of induced hypertension is associated with fibrosis, vascular wall thickening, and carotid plaque development, which might impair endothelium-independent vasorelaxation and vasa vasorum growth leading to carotid plaque development. 11 From the 8th to the 12th month in the current study, the plaque scores in the constriction group were all significantly higher than in the sham group, and 12 months after clip placement carotid plaque formation was proven by digital subtraction angiography and histological examination.…”

“…11 These results indicate that 3 to 4 months of induced hypertension is associated with fibrosis, vascular wall thickening, and carotid plaque development, which might impair endothelium-independent vasorelaxation and vasa vasorum growth leading to carotid plaque development. 11 From the 8th to the 12th month in the current study, the plaque scores in the constriction group were all significantly higher than in the sham group, and 12 months after clip placement carotid plaque formation was proven by digital subtraction angiography and histological examination. Also in the present study, biochemical parameters were not different between the groups at the indicated time points, suggesting that the plaque formation was not caused by chronic elevation of these factors.…”

Hypercholesterolemia and Hypertension: Two Sides of the Same Coin

“…Versari et al [37] in experimental research in an animal model confirmed a different influence of hypercholesterolemia and hypertension on the structural and functional changes of the carotid arteries. They found that both risk factors induced an increase in systemic and vascular oxidative stress, with a consequent reduction in vasorelaxation.…”