BACKGROUND: Oxidized LDL has been found within the subendothelial space, and it exhibits numerous atherogenic properties, including induction of inflammatory genes. We examined the possibility that variations in endothelial response to minimally modified LDL (MM-LDL) constitute one of the genetic components in atherosclerosis. METHODS AND RESULTS: By a novel explant technique, endothelial cells (ECs) were isolated from the aorta of inbred mouse strains with different susceptibilities to diet-induced atherosclerosis. Responses to MM-LDL were evaluated by examining the expression of inflammatory genes involved in atherosclerosis, including monocyte chemotactic protein-1 (MCP-1) and macrophage-colony-stimulating factor (M-CSF), an oxidative stress gene, heme oxygenase-1 (HO-1), and other, noninflammatory, genes. ECs from the susceptible mouse strain C57BL/6J exhibited dramatic induction of MCP-1, M-CSF, and HO-1, whereas ECs from the resistant strain C3H/HeJ showed little or no induction. In contrast, ECs from the 2 strains responded similarly to lipopolysaccharide. CONCLUSIONS: These data provide strong evidence that genetic factors in atherosclerosis act at the level of the vessel wall.
BACKGROUND: Oxidized LDL has been found within the subendothelial space, and it exhibits numerous atherogenic properties, including induction of inflammatory genes. We examined the possibility that variations in endothelial response to minimally modified LDL (MM-LDL) constitute one of the genetic components in atherosclerosis. METHODS AND RESULTS: By a novel explant technique, endothelial cells (ECs) were isolated from the aorta of inbred mouse strains with different susceptibilities to diet-induced atherosclerosis. Responses to MM-LDL were evaluated by examining the expression of inflammatory genes involved in atherosclerosis, including monocyte chemotactic protein-1 (MCP-1) and macrophage-colony-stimulating factor (M-CSF), an oxidative stress gene, heme oxygenase-1 (HO-1), and other, noninflammatory, genes. ECs from the susceptible mouse strain C57BL/6J exhibited dramatic induction of MCP-1, M-CSF, and HO-1, whereas ECs from the resistant strain C3H/HeJ showed little or no induction. In contrast, ECs from the 2 strains responded similarly to lipopolysaccharide. CONCLUSIONS: These data provide strong evidence that genetic factors in atherosclerosis act at the level of the vessel wall.
Authors: Peter S Gargalovic; Minori Imura; Bin Zhang; Nima M Gharavi; Michael J Clark; Joanne Pagnon; Wen-Pin Yang; Aiqing He; Amy Truong; Shilpa Patel; Stanley F Nelson; Steve Horvath; Judith A Berliner; Todd G Kirchgessner; Aldons J Lusis Journal: Proc Natl Acad Sci U S A Date: 2006-08-15 Impact factor: 11.205
Authors: Filip K Swirski; Peter Libby; Elena Aikawa; Pilar Alcaide; F William Luscinskas; Ralph Weissleder; Mikael J Pittet Journal: J Clin Invest Date: 2007-01 Impact factor: 14.808
Authors: Pinaki Chaudhuri; Scott M Colles; Manjunatha Bhat; David R Van Wagoner; Lutz Birnbaumer; Linda M Graham Journal: Mol Biol Cell Date: 2008-05-21 Impact factor: 4.138