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- Title
Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice.
- Authors
Yuki Hirano; Choi, Alex; Masashi Tsuruta; Jen Erh Jaw; Yeni Oh; Ngan, David; Konosuke Moritani; Yu-Wei Roy Chen; Sheena Tam; Yuexin Li; Vasilescu, Dragoş M.; Hogg, James C.; Francis, Gordon; Bernatchez, Pascal; Shu-Fan Paul Man; Sin, Don D.
- Abstract
Aims Although surfactant protein-D (SP-D) is a pneumoprotein that is predominantly synthesized by type II epithelial cells in the lung, individuals with increased circulating levels of SP-D are at an elevated risk of mortality from ischemic heart disease. Whether SP-D contributes directly to atherosclerosis is unknown. We determined the effects of SP-D gene deletion in a mouse model of atherosclerosis. Methods and results SP-D knockout (KO) mice were crossed with hyperlipidemic and atherosclerosis-prone apolipoprotein E (ApoE) KO mice to generate SP-D/ApoE double knockout (DKO) mice. Mice were placed on a high-fat diet for 12 weeks beginning at 8 weeks of age. Compared with ApoE KO mice, SP-D/ApoE DKO mice had significantly less atherosclerosis with reduced macrophage accumulation, decreased local macrophage proliferation, and increased smooth muscle cell coverage in plaques. Interestingly, SP-D deficiency worsened hypercholesterolemia and induced obesity and insulin resistance but suppressed plasma interleukin-6 (IL-6) levels. SP-D deficiency also reduced blood monocytes and neutrophils counts in ApoE KO mice. Conclusion SP-D deficiency reduces atherosclerosis in part by decreasing the accumulation and proliferation of macrophages and by reducing IL-6 levels systemically. SP-D is a promising therapeutic target for cachectic COPD patients with elevated circulating SP-D levels who are at increased risk of cardiovascular morbidity and mortality.
- Subjects
PULMONARY surfactant-associated protein D; INFLAMMATION; ATHEROSCLEROSIS; LABORATORY mice; APOLIPOPROTEIN E; INTERLEUKIN-6
- Publication
Cardiovascular Research, 2017, Vol 113, Issue 10, p1208
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1093/cvr/cvx067