title: LOX-1 deletion limits cardiac angiogenesis in mice given angiotensin II.
abstract: Lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1) is a major receptor for ox-LDL in endothelial cells. Its activation regulates endothelial proliferation, differentiation, migration and apoptosis. Recent in vitro studies show that LOX-1 activation by ox-LDL and angiotensin II (Ang II) induces angiogenesis via activation of NADPH oxidase and subsequent increase in ROS production. In this study, we investigated the effect of LOX-1 gene deletion (LOX-1 knockout or KO mice) on angiogenesis in response to prolonged Ang II infusion in vivo. Our studies showed that Ang II (vs. saline) infusion enhanced capillary formation in subcutaneously injected Matrigel® plugs. Ang II infusion also resulted in marked angiogenesis in the hearts as determined by CD31 immunopositivity. There was an increased expression (RT-PCR and Western blotting) of CD31 and VEGF in the hearts of mice infused with Ang II, indicating pro-angiogenic miliue. More importantly, LOX-1 KO mice reveled markedly limited angiogenesis in the Matrigel® plugs as well as in the hearts despite similar infusion with Ang II (all P < 0.05 vs. wild-type mice). In addition, the hearts of LOX-1 KO mice had attenuated expression of pro-inflammatory and angiogenic signals MCP-1 and IL-1β following Ang II Infusion. Lastly, the rise in blood pressure in response to Ang II was less in the LOX-1 KO mice (P < 0.05 vs. wild-type mice). Our findings suggest that LOX-1 participates in angiogenesis in hypertension, which may be related to a state of inflammation.
authors.affiliation: Department of Medicine, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, AR, 72212, USA, XWang2@UAMS.edu.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.forename: Magomed
authors.initials: M
authors.lastname: Khaidakov
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Guo
authors.forename: Zufeng
authors.initials: Z
authors.lastname: Ding
authors.forename: Quanzhong
authors.initials: Q
authors.lastname: He
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D003094:Collagen / Q000502:physiology; D004338:Drug Combinations; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D007797:Laminin / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011509:Proteoglycans / Q000502:physiology; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004338:Drug Combinations; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D007797:Laminin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011509:Proteoglycans; D051127:Scavenger Receptors, Class E; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000804:Angiotensin II; C059485:matrigel; D003094:Collagen