title: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and cardiac fibroblast growth.
abstract: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) regulates growth of a variety of cells and is important in inflammation, oxidative stress, and tissue remodeling. Recent studies show that LOX-1 deletion limits cardiac remodeling after sustained hypertension. We posited that LOX-1 may affect cardiac fibroblast growth and collagen secretion. To examine this postulate, we studied growth pattern of cardiac fibroblasts from hearts of wild-type and LOX-1 knockout (KO) mice. LOX-1 KO fibroblasts exhibited dramatically reduced growth when compared with wild-type mice fibroblasts and became much larger than wild-type mice fibroblasts in serial cultures, suggesting arrest of cell division. Western blotting and immunofluorescence showed that cell division control protein 42, a key regulator for cell division, was markedly downregulated in LOX-1 KO fibroblasts. The cytoskeletal organization in these fibroblasts was significantly altered in strand orientation, and some fibroblasts were completely devoid of F-actin. Furthermore, NADPH oxidase expression and generation of reactive oxygen species, as well as cell proliferation signals serine/threonine-specific protein kinase and murine double minute 2, were significantly reduced in LOX-1 KO fibroblasts. To confirm the essential role of LOX-1 in fibroblast growth, LOX-1 KO fibroblasts were transfected with h-LOX-1 cDNA. After transfection, the altered pattern of cytoskeletal organization, as well as expression of cell division control protein 42, serine/threonine-specific protein kinase, and murine double minute 2, was normalized. In congruent with these in vitro data, we found that the cardiac fibroblast number and expression of fibronectin and procoallagen-1/collagen were significantly lower in hypertensive LOX-1 KO mice hearts than in hypertensive wild-type mice hearts subjected to sustained hypertension (angiotensin II infusion). These findings implicate LOX-1 in cytoskeletal organization and growth of cardiac fibroblasts.
authors.affiliation: Central Arkansas Veterans Healthcare System and Division of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR 72212, USA.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.forename: Magomed
authors.initials: M
authors.lastname: Khaidakov
authors.forename: Zufeng
authors.initials: Z
authors.lastname: Ding
authors.forename: Sona
authors.initials: S
authors.lastname: Mitra
authors.forename: Jingjun
authors.initials: J
authors.lastname: Lu
authors.forename: Yao
authors.initials: Y
authors.lastname: Dai
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000502:physiology*; D049108:Cell Enlargement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000199:Actins; C495138:Olr1 protein, mouse; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; D003094:Collagen; D019255:NADPH Oxidases; D051057:Proto-Oncogene Proteins c-akt