Allergic asthma aggravated atherosclerosis increases cholesterol biosynthesis and foam cell formation in apolipoprotein E-deficient mice.

Abstract

Several studies have demonstrated that allergic asthma can induce atherosclerosis formation in mice. Moreover, allergic asthma and atherosclerosis have been shown to be strongly associated with dyslipidemia. In this study, we investigated the underlying mechanism of allergic asthma-aggravated atherosclerosis-induced cholesterol metabolism disorder in asthmatic apoE-/- mice. We found that allergic asthma increased the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the liver and CD36 in the aorta during the acute and advanced stages of atherosclerosis, respectively. These results indicate that cholesterol biosynthesis is increased during acute atherosclerosis and cholesterol uptake and foam cell formation is increased during advanced atherosclerosis. Simvastatin administration significantly ameliorated the aortic root lesion size of asthmatic mice and significantly decreased HMGCR and CD36 expression. However, the expression of the low-density lipoprotein receptor and ATP-binding cassette transporter A1 was markedly increased, indicating that the beneficial effect of statins in allergic asthma and coronary artery disease was mediated, at least in part, by decreasing cholesterol biosynthesis and foam cell formation. In conclusion, allergic asthma aggravates atherosclerosis by regulating cholesterol metabolism in apoE-/- mice. Allergic asthma selectively promotes cholesterol biosynthesis in acute atherosclerosis and increases foam cell formation in advanced atherosclerosis.

• Authors: Shanshan Gao, Chen Wang, Wenyuan Li, Shan Shu, Juan Zhou, Zuyi Yuan, Lijun Wang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 519 Issue 4 Pg. 861-867 (11 19 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 31558320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Apolipoproteins E
• Cholesterol

Topics

• Animals
• Apolipoproteins E (deficiency, metabolism)
• Asthma (metabolism)
• Atherosclerosis (metabolism, pathology)
• Cholesterol (biosynthesis)
• Disease Models, Animal
• Dyslipidemias (blood, metabolism)
• Foam Cells (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout