|Title||Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Hirano, Y, Choi, A, Tsuruta, M, Jaw, JE, Oh, Y, Ngan, D, Moritani, K, Chen, YR, Tam, S, Li, Y, Vasilescu, DM, Hogg, JC, Francis, G, Bernatchez, P, Man, SP, Sin, D|
|ISSN||Print: 0008-6363; Online: 1755-3245|
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.
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.