دورية أكاديمية
Macrophage angiotensin-converting enzyme reduces atherosclerosis by increasing peroxisome proliferator-activated receptor α and fundamentally changing lipid metabolism
| العنوان: | Macrophage angiotensin-converting enzyme reduces atherosclerosis by increasing peroxisome proliferator-activated receptor α and fundamentally changing lipid metabolism |
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| المؤلفون: | Cao, DuoYao, Khan, Zakir, Li, Xiaomo, Saito, Suguru, Bernstein, Ellen A, Victor, Aaron R, Ahmed, Faizan, Hoshi, Aoi O, Veiras, Luciana C, Shibata, Tomohiro, Che, Mingtian, Cai, Lei, Yamashita, Michifumi, Temel, Ryan E, Giani, Jorge F, Luthringer, Daniel J, Divakaruni, Ajit S, Okwan-Duodu, Derick, Bernstein, Kenneth E |
| المساهمون: | AHA, NIH |
| المصدر: | Cardiovascular Research ; volume 119, issue 9, page 1825-1841 ; ISSN 0008-6363 1755-3245 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2023 |
| الوصف: | Aims The metabolic failure of macrophages to adequately process lipid is central to the aetiology of atherosclerosis. Here, we examine the role of macrophage angiotensin-converting enzyme (ACE) in a mouse model of PCSK9-induced atherosclerosis. Methods and results Atherosclerosis in mice was induced with AAV-PCSK9 and a high-fat diet. Animals with increased macrophage ACE (ACE 10/10 mice) have a marked reduction in atherosclerosis vs. WT mice. Macrophages from both the aorta and peritoneum of ACE 10/10 express increased PPARα and have a profoundly altered phenotype to process lipids characterized by higher levels of the surface scavenger receptor CD36, increased uptake of lipid, increased capacity to transport long chain fatty acids into mitochondria, higher oxidative metabolism and lipid β-oxidation as determined using 13C isotope tracing, increased cell ATP, increased capacity for efferocytosis, increased concentrations of the lipid transporters ABCA1 and ABCG1, and increased cholesterol efflux. These effects are mostly independent of angiotensin II. Human THP-1 cells, when modified to express more ACE, increase expression of PPARα, increase cell ATP and acetyl-CoA, and increase cell efferocytosis. Conclusion Increased macrophage ACE expression enhances macrophage lipid metabolism, cholesterol efflux, efferocytosis, and it reduces atherosclerosis. This has implications for the treatment of cardiovascular disease with angiotensin II receptor antagonists vs. ACE inhibitors. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/cvr/cvad082 |
| DOI: | 10.1093/cvr/cvad082/50562489/cvad082.pdf |
| الإتاحة: | https://doi.org/10.1093/cvr/cvad082Test https://academic.oup.com/cardiovascres/article-pdf/119/9/1825/56541501/cvad082.pdfTest |
| حقوق: | https://academic.oup.com/pages/standard-publication-reuse-rightsTest |
| رقم الانضمام: | edsbas.BB4F3E25 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/cvr/cvad082 |
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