Pharmaceutical stabilization of mast cells attenuates experimental atherogenesis in low-density lipoprotein receptor-deficient mice
| Autor: | Blandine Secco, Jing Wang, Guo-Ping Shi, Sara Sjöberg, Han Chen, Viviane Tia, Min Yang, Galina K. Sukhova |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Vasculitis medicine.medical_specialty Inflammation Anti-asthmatic Agent Article Lesion Mice chemistry.chemical_compound Internal medicine Cromolyn Sodium medicine Animals p-Methoxy-N-methylphenethylamine Anti-Asthmatic Agents Mast Cells Triglycerides Mice Knockout Triglyceride business.industry Atherosclerosis Mast cell Lipoproteins LDL Mice Inbred C57BL Disease Models Animal Endocrinology medicine.anatomical_structure Receptors LDL chemistry LDL receptor lipids (amino acids peptides and proteins) medicine.symptom Cardiology and Cardiovascular Medicine business Lipoprotein |
| Zdroj: | Atherosclerosis. 229:304-309 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/j.atherosclerosis.2013.05.025 |
| Popis: | Mast cells (MCs) contribute to atherogenesis by releasing pro-inflammatory mediators to activate vascular cells and other inflammatory cells. This study examined whether MC activation or stabilization affects diet-induced atherosclerosis in low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice. When Ldlr(-/-) mice consumed an atherogenic diet for 3 or 6 months, MC activation with compound 48/80 (C48/80) increased aortic arch intima and total lesion areas, and plasma total cholesterol, LDL, and triglyceride levels, whereas MC stabilization with cromolyn reduced these parameters. There were significant differences in arch intima and total lesion areas, and plasma total cholesterol, LDL, and triglyceride levels between C48/80-treated and cromolyn-treated mice. To examine a therapeutic application of cromolyn in atherosclerosis, we fed Ldlr(-/-) mice an atherogenic diet for 3 months followed by giving mice cromolyn for additional 3 months. Cromolyn did not affect aortic arch intima area, but significantly reduced lipid deposition in the thoracic-abdominal aortas. In aortic arches, however, cromolyn treatment significantly reduced lesion contents of Mac-3(+) macrophages, CD4(+) T cells, activated MCs, and lesion cell proliferation. While plasma total cholesterol and LDL levels increased and high-density lipoprotein (HDL) levels decreased from 3 months to 6 months of an atherogenic diet, cromolyn treatment decreased significantly plasma total cholesterol, LDL, and triglyceride levels and increased HDL levels above those of 3-month time point. These observations demonstrate that MC stabilization reduces lesion inflammation, ameliorates plasma lipid profiles, and may serve as a potential therapy for this cardiovascular disease. |
| Databáze: | OpenAIRE |
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