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.

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