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

Yuki Hirano, Alex Choi, Masashi Tsuruta, Jen Erh Jaw, Yeni Oh, David Ngan, Konosuke Moritani, Yu Wei Roy Chen, Sheena Tam, Yuexin Li, Dragoş M. Vasilescu, James C. Hogg, Gordon Francis, Pascal Bernatchez, Shu Fan Paul Man, Don D. Sin

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1208-1218
Number of pages11
JournalCardiovascular Research
Volume113
Issue number10
DOIs
Publication statusPublished - 2017 Aug 1

Keywords

  • Apolipoprotein E
  • Atherosclerosis
  • IL-6
  • Macrophage
  • Surfactant protein D

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Hirano, Y., Choi, A., Tsuruta, M., Jaw, J. E., Oh, Y., Ngan, D., Moritani, K., Chen, Y. W. R., Tam, S., Li, Y., Vasilescu, D. M., Hogg, J. C., Francis, G., Bernatchez, P., Man, S. F. P., & Sin, D. D. (2017). Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice. Cardiovascular Research, 113(10), 1208-1218. https://doi.org/10.1093/cvr/cvx067