High-Density Lipoprotein Abnormalities Due to Scavenger Receptor Class B Type I Dysfunction Led to Proteinuria and Glomerular Lipidosis in Atherosclerosis-Prone Mice
28 Pages Posted: 23 Mar 2019More...
Background: Scavenger receptor class B type I (SR-BI) is the major high-density lipoprotein (HDL) receptor in mammalians, whose dysfunction leads to various aspects of HDL abnormalities and subsequent cardiovascular disorders. However, whether HDL abnormalities due to SR-BI dysfunction could cause renal functional or histopathological changes are not defined.
Methods: Plasma lipids, renal functions and histopathology were analyzed in SR-BI knockout (KO) mice and low-density lipoprotein receptor (Ldl-r) KO mice with SR-BI deletion on chow diet or a high-fat diet (HFD) for 12 weeks.
Findings: HDL particles from SR-BI KO mice presented with higher free cholesterol content and enlarged sizes on chow diet, which were aggravated by HFD feeding. HDL abnormalities did not cause significant renal functional or histopathological alterations in SR-BI KO mice on chow diet or HFD. However, HDL abnormalities due to SR-BI dysfunction increased urinary protein content and caused mild glomerular lipidosis in Ldl-r KO mice on chow diet, which were progressed into severe proteinuria and extensive glomerular lipidosis after HFD challenge.
Interpretation: HDL abnormalities due to SR-BI dysfunction led to spontaneous and diet-exacerbated proteinuria and glomerular lipidosis in atherosclerosis-prone mice, suggesting SR-BI dysfunction might be a potent risk factor for atherosclerotic nephropathy in hypercholesterolemic patients. Moreover, SR-BI/Ldl-r double KO mice might be used as a unique murine model to study the relationship between glomerular lipidosis and atherosclerotic cardiovascular diseases.
Funding: This study was supported by the Youth Science Fund Program of National Natural Science Foundation of China and the National Natural Science Foundation of China.
Declaration of Interest: All the authors declared no competing interests.
Ethical Approval: All experimental procedures were in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institute of Health and approved by the Animal Care Committee at Peking University.
Keywords: SR-BI; HDL; Proteinuria; Glomerular lipidosis; High-fat diet
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