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

Cardiovasc Res. 2017 Aug 1;113(10):1208-1218. doi: 10.1093/cvr/cvx067.


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.

Keywords: Apolipoprotein E; Atherosclerosis; IL-6; Macrophage; Surfactant protein D.

MeSH terms

  • Animals
  • Aorta / metabolism
  • Aorta / pathology
  • Aortic Diseases / genetics
  • Aortic Diseases / metabolism
  • Aortic Diseases / pathology
  • Aortic Diseases / prevention & control*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Cell Proliferation
  • Disease Models, Animal
  • Genetic Predisposition to Disease
  • Hypercholesterolemia / genetics
  • Hypercholesterolemia / metabolism
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Insulin Resistance / genetics
  • Interleukin-6 / blood
  • Macrophage Activation
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology
  • Obesity / genetics
  • Obesity / metabolism
  • Phenotype
  • Plaque, Atherosclerotic*
  • Pulmonary Surfactant-Associated Protein D / deficiency*
  • Pulmonary Surfactant-Associated Protein D / genetics


  • Interleukin-6
  • Pulmonary Surfactant-Associated Protein D
  • interleukin-6, mouse