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

6 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
Externally publishedYes

Fingerprint

Pulmonary Surfactant-Associated Protein D
Protein Deficiency
Apolipoproteins E
Knockout Mice
Atherosclerosis
Inflammation
Macrophages
Interleukin-6
Mortality
Gene Deletion
High Fat Diet
Hypercholesterolemia
Chronic Obstructive Pulmonary Disease
Smooth Muscle Myocytes
Myocardial Ischemia
Insulin Resistance

Keywords

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

ASJC Scopus subject areas

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

Cite this

Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice. / Hirano, Yuki; Choi, Alex; Tsuruta, Masashi; Jaw, Jen Erh; Oh, Yeni; Ngan, David; Moritani, Konosuke; Chen, Yu Wei Roy; Tam, Sheena; Li, Yuexin; Vasilescu, Dragoş M.; Hogg, James C.; Francis, Gordon; Bernatchez, Pascal; Man, Shu Fan Paul; Sin, Don D.

In: Cardiovascular Research, Vol. 113, No. 10, 01.08.2017, p. 1208-1218.

Research output: Contribution to journalArticle

Hirano, Y, Choi, A, Tsuruta, M, Jaw, JE, Oh, Y, Ngan, D, Moritani, K, Chen, YWR, Tam, S, Li, Y, Vasilescu, DM, Hogg, JC, Francis, G, Bernatchez, P, Man, SFP & Sin, DD 2017, 'Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice', Cardiovascular Research, vol. 113, no. 10, pp. 1208-1218. https://doi.org/10.1093/cvr/cvx067
Hirano, Yuki ; Choi, Alex ; Tsuruta, Masashi ; Jaw, Jen Erh ; Oh, Yeni ; Ngan, David ; Moritani, Konosuke ; Chen, Yu Wei Roy ; Tam, Sheena ; Li, Yuexin ; Vasilescu, Dragoş M. ; Hogg, James C. ; Francis, Gordon ; Bernatchez, Pascal ; Man, Shu Fan Paul ; Sin, Don D. / Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice. In: Cardiovascular Research. 2017 ; Vol. 113, No. 10. pp. 1208-1218.
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AU - Tsuruta, Masashi

AU - Jaw, Jen Erh

AU - Oh, Yeni

AU - Ngan, David

AU - Moritani, Konosuke

AU - Chen, Yu Wei Roy

AU - Tam, Sheena

AU - Li, Yuexin

AU - Vasilescu, Dragoş M.

AU - Hogg, James C.

AU - Francis, Gordon

AU - Bernatchez, Pascal

AU - Man, Shu Fan Paul

AU - Sin, Don D.

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N2 - 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.

AB - 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.

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