| First Author | Hirano Y | Year | 2017 |
| Journal | Cardiovasc Res | Volume | 113 |
| Issue | 10 | Pages | 1208-1218 |
| PubMed ID | 28472244 | Mgi Jnum | J:258824 |
| Mgi Id | MGI:6141220 | Doi | 10.1093/cvr/cvx067 |
| Citation | Hirano Y, et al. (2017) Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice. Cardiovasc Res 113(10):1208-1218 |
| abstractText | 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. |
