Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice

TitleSurfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice
Publication TypeJournal Article
Year of Publication2017
AuthorsHirano, 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
JournalCardiovascular Research
Volume113
Issue10
Pagination1208-1218
Date Published08/2017
ISSNPrint: 0008-6363; Online: 1755-3245
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.

DOI10.1093/cvr/cvx067