Abstract
Endothelial dysfunction is recognized as a major contributor to atherosclerosis and has been suggested to be evident far before plaque formation. Endothelial dysfunction in small resistance arteries has been suggested to initiate long before changes in conduit arteries. In this study, we address early changes in endothelial function of atherosclerosis prone rats. Male ApoE knockout (KO) rats (11- to 13-weeks-old) were subjected to either a Western or standard diet. The diet intervention continued for a period of 20–24 weeks. Endothelial function of pulmonary and mesenteric arteries was examined in vitro using an isometric myograph. We found that Western diet decreased the contribution of cyclooxygenase (COX) to control the vascular tone of both pulmonary and mesenteric arteries. These changes were associated with early stage atherosclerosis and elevated level of plasma total cholesterol, LDL and triglyceride in ApoE KO rats. Chondroid-transformed smooth muscle cells, calcifications, macrophages accumulation and foam cells were also observed in the aortic arch from ApoE KO rats fed Western diet. The ApoE KO rats are a new model to study endothelial dysfunction during the earlier stages of atherosclerosis and could help us improve preclinical drug development.
Highlights
Endothelial dysfunction is recognized as a major contributor to atherosclerosis and has been suggested to be evident far before plaque formation
At the end of the study, at the age of 31–37 weeks; body weight increased significantly in all groups; (661.0 ± 55.40 g) in Apolipoprotein knockout (ApoE KO) on Western diet, (586.30 ± 67.69 g) in ApoE KO on standard diet and (574.0 ± 10.77 g) in the Sprague Dawley rats on standard diet (P < 0.0001)
The increase in weight was greater in ApoE KO on a Western diet and there was a significant difference in body weight between this group and ApoE KO and Sprague Dawley rats on a standard diet (P = 0.0005)
Summary
Endothelial dysfunction is recognized as a major contributor to atherosclerosis and has been suggested to be evident far before plaque formation. We found that Western diet decreased the contribution of cyclooxygenase (COX) to control the vascular tone of both pulmonary and mesenteric arteries. These changes were associated with early stage atherosclerosis and elevated level of plasma total cholesterol, LDL and triglyceride in ApoE KO rats. The ApoE KO rats are a new model to study endothelial dysfunction during the earlier stages of atherosclerosis and could help us improve preclinical drug development. Endothelial dysfunction in small resistance arteries has been suggested to initiate long before changes in conduit a rteries[10,11,12]. There are no comprehensive reports that characterise the vascular properties of ApoE KO rats
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