regional gene expression of lox-1, vcam-1, and icam-1 in aorta of hiv-1 transgenic rats区域基因表达lox-1、vcam-1 icam-1 hiv - 1转基因大鼠的主动脉.pdfVIP

Regional Gene Expression of LOX-1, VCAM-1, and ICAM-1 in Aorta of HIV-1 Transgenic Rats Anne Mette Fisker Hag1,2*, Ulrik Sloth Kristoffersen1,2, Sune Folke Pedersen1,2, Henrik Gutte1,2, Anne- Mette Lebech3, Andreas Kjaer1,2 1 Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark, 2 Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen, Denmark, 3 Department of Infectious Diseases, Hvidovre Hospital, Hvidovre, Denmark Abstract Background: Increased prevalence of atherosclerotic cardiovascular disease in HIV-infected patients has been observed. The cause of this accelerated atherosclerosis is a matter of controversy. As clinical studies are complicated by a multiplicity of risk-factors and a low incidence of hard endpoints, studies in animal models could be attractive alternatives. Methodology/Principal Findings: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in HIV-1 transgenic (HIV-1Tg) rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1 was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups. Conclusions/Significance: HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular dis