AI Article Synopsis
- Excessive cholesterol is a major risk factor for vascular disease, with its distribution in cells varying between detergent-sensitive and detergent-resistant fractions, primarily located in cellular membranes.
- A study on male Sprague-Dawley rats fed a high-cholesterol diet revealed that the aorta and cerebral arteries showed the most significant cholesterol accumulation, particularly in non-esterified forms, during specific weeks of the diet.
- The differential accumulation of cholesterol in various arteries correlates with the up-regulation of genes involved in cholesterol uptake, indicating that certain arteries, like the cerebral artery, are more susceptible to cholesterol than others, such as the pulmonary and mesenteric arteries.
Article Abstract
Excessive cholesterol constitutes a major risk factor for vascular disease. Within cells, cholesterol is distributed in detergent-sensitive and detergent-resistant fractions, with the largest amount of cholesterol residing in cellular membranes. We set out to determine whether various arteries differ in their ability to accumulate esterified and non-esterified cholesterol in detergent-sensitive versus detergent-resistant fractions throughout the course of a high-cholesterol diet. Male Sprague-Dawley rats were placed on 2 % cholesterol diet while a control group was receiving iso-caloric standard chow. Liver, aorta, and pulmonary, mesenteric, and cerebral arteries were collected at 2-6, 8-12, 14-18, and 20-24 weeks from the start of high-cholesterol diet. After fraction separation, esterified and free non-esterified cholesterol levels were measured. In all arteries, largest cholesterol amounts were present in detergent-sensitive fractions in the non-esterified form. Overall, cholesterol in aorta and cerebral arteries was elevated during 14-18 weeks of high-cholesterol diet. Cerebral arteries also exhibited increase in esterified cholesterol within detergent-sensitive domains, as well as increase in cholesterol level in the detergent-resistant fraction at earlier time-points of diet. Pulmonary artery and mesenteric artery were largely resistant to cholesterol accumulation. Quantitative polymerase chain reaction (qPCR) analysis revealed up-regulation of low-density lipoprotein receptor (Ldlr) and low-density lipoprotein receptor-related protein 1 (Lrp1) gene expression in cerebral arteries when compared to mesenteric and pulmonary arteries, respectively. In summary, we unveiled the differential ability of arteries to accumulate cholesterol over the course of a high-cholesterol diet. The differential accumulation of cholesterol seems to correlate with the up-regulated gene expression of proteins responsible for cholesterol uptake.
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| http://dx.doi.org/10.1016/j.bbalip.2022.159235 | DOI Listing |
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