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Published on: May 15, 2020
Arterial endothelial function in a porcine model of early stage atherosclerotic vascular disease
James R Turk1, Kyle K Henderson, Gregory D Vanvickle
1Department of Biomedical Sciences, College of Veterinary Medicine, Columbia, MO 65211, USA. turkj@missouri.edu
Insights
High-fat, cholesterol diets cause early atherosclerosis in pigs, leading to vascular disease in some arteries before affecting blood vessel function. Early atherosclerosis stages precede endothelial dysfunction in certain arteries.
Area of Science:
- Cardiovascular Science
- Vascular Biology
- Atherosclerosis Research
Background:
- Cardiovascular disease (CVD) is a major global health concern, with atherosclerosis as a primary contributor.
- Understanding the early stages of atherosclerosis and its impact on vascular function is crucial for disease prevention and treatment.
Purpose of the Study:
- To investigate the relationship between diet-induced endothelial dysfunction and early-stage atherosclerotic vascular disease.
- To test the hypothesis that hypercholesterolemia impairs endothelium-dependent relaxation (EDR) in conduit arteries.
Main Methods:
- Adult male Yucatan pigs were fed either a normal fat (NF) or high-fat cholesterol (HFC) diet for 20-24 weeks.
- Vascular function (EDR) and histopathological changes (fatty streaks, intima-media thickness, foam cell accumulation) were assessed in various arteries.
Main Results:
- The HFC diet induced atherosclerosis, characterized by fatty streaks and increased intima-media thickness (IMT) in the aorta, carotid, and femoral arteries.
- Endothelium-dependent relaxation (EDR) was significantly decreased in carotid and coronary arteries but not in femoral or brachial arteries.
- Femoral arteries showed atherosclerotic changes (foam cells, increased IMT) without impaired EDR, indicating early vascular disease precedes endothelial dysfunction in these vessels.
Conclusions:
- Early stages of atherosclerosis (Stary Stage I-III) can develop in specific arteries before significant endothelial dysfunction is observed.
- Diet-induced hypercholesterolemia impacts vascular disease progression differently across arterial beds.
- These findings highlight the complex interplay between atherosclerosis development and endothelial function in the early stages of CVD.
Abstract:
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States and is projected to become the leading cause of mortality in the world. Atherosclerosis is the most important single factor contributing to this disease burden. In this study, we characterize relationships between endothelial dysfunction and vascular disease in an animal model of diet-induced, early-stage atherosclerotic vascular disease. We tested the hypothesis that hypercholesterolaemia induces vascular disease and impairs endothelium-dependent relaxation (EDR) in conduit arteries of adult male Yucatan pigs. Pigs were fed a normal fat (NF) or high fat cholesterol (HFC) diet for 20-24 weeks. Results indicate that, while the HFC diet did not alter EDR in femoral or brachial arteries, EDR was significantly decreased in both carotid and coronary arteries. Sudanophilic fatty streaks were significantly present in the abdominal aorta and common carotid artery. Histopathology revealed increased intima-media thickness (IMT) and foam cell accumulation in Stary Stage I-III lesions in the abdominal aorta, common carotid artery and femoral arteries. In the coronary arteries, the accumulation of foam cells in Stary Stage I and II lesions resulted in a trend for increased IMT. There was no evidence of vascular disease in the brachial arteries. These results indicate that early stages of CVD (Stary Stage I-III) precede decreases in EDR induced by HFC diet, because femoral arteries exhibited foam cell accumulation and an increased IMT but no change in endothelial function.

