title: Nifedipine inhibits ox-LDL-induced lipid accumulation in human blood-derived macrophages.
abstract: Studies have shown that nifedipine, an anti-hypertensive drug, protects against atherosclerotic progression, but the underlying mechanisms remain elusive. Oxidized low-density lipoprotein (ox-LDL) is critically implicated in macrophage lipid deposition seen in atherosclerosis. In this study, we examined the effects of nifedipine on some ox-LDL-associated changes in human blood-derived macrophages. We isolated monocytes from normal human blood and differentiated them into macrophages. We then treated these human macrophages with ox-LDL and/or nifedipine, and examined lipid accumulation and expression levels of two scavenge receptors CD36 and SR-A as well as a protein kinase PKC-θ. Nifedipine treatment substantially reduced lipid accumulation and the expression of CD36, SR-A, and protein kinase C (PKC)-θ in human macrophages treated with ox-LDL. Silencing of PKC-θ using siRNA also reduced the expression of CD36 and SR-A in these cells. Our results thus suggest that nifedipine may inhibit atherosclerosis by reducing ox-LDL-induced lipid deposition through suppression of the CD36/SR-A-mediated uptake of ox-LDL by macrophages via a PKC-θ-dependent mechanism.
authors.affiliation: Department of Cardiology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China; Department of Animal and Avian Sciences, Uiniversity of Maryland, College Park, MD 20740, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: A Zhi
authors.initials: AZ
authors.lastname: Sha Ma
authors.affiliation: Department of Cardiology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Animal and Avian Sciences, Uiniversity of Maryland, College Park, MD 20740, USA.
authors.forename: Wei-Qing
authors.initials: WQ
authors.lastname: Tang
authors.affiliation: Department of Cardiology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China. Electronic address: zysong2010@126.com.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Song
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism / Q000517:prevention & control; D018955:CD36 Antigens / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000074121:Protein Kinase C-theta; D034741:RNA, Small Interfering / Q000235:genetics; D051117:Scavenger Receptors, Class A / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D002121:Calcium Channel Blockers; D007527:Isoenzymes; D008077:Lipoproteins, LDL; D034741:RNA, Small Interfering; D051117:Scavenger Receptors, Class A; C099252:oxidized low density lipoprotein; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D009543:Nifedipine
keywords: CD36; Nifedipine; Ox-LDL; PKC-θ; SR-A; siRNA