Myocardial hypoxia-inducible HIF-1 , VEGF, and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia
نویسندگان
چکیده
Bateman RM, Tokunaga C, Kareco T, Dorscheid DR, Walley KR. Myocardial hypoxia-inducible HIF-1 , VEGF, and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia. Am J Physiol Heart Circ Physiol 293: H448–H456, 2007. First published March 16, 2007; doi:10.1152/ajpheart.00035.2007.—The systemic inflammatory response to infection is the leading cause of mortality in North American intensive-care units. Although much is known about inflammatory mediators, the relationships between microregional inflammation, microvascular heterogeneity, hypoxia, hypoxia-inducible gene expression, and myocardial dysfunction are unknown. Male Sprague-Dawley rats were injected intraperitoneally with LPS to test the hypothesis that sepsis-induced local inflammation and increased microvascular heterogeneity are spatially and temporally associated with hypoxia, hypoxia-inducible gene expression, and decreased left-ventricular contractility. Using a combination of threedimensional microvascular imaging, tissue PO2, and pressure-volume conductance measurements, we found that 5 h after LPS, minimum oxygen-diffusion distances increased (P 0.05), whereas tissue oxygenation and contractility both decreased (P 0.05) in the left ventricle. Real-time RT-PCR analysis revealed that the hypoxiainducible genes hypoxia-inducible factor (HIF)-1 , VEGF, and glucose transporter (GLUT) 1 were all upregulated (P 0.05) in the left ventricle. Tissue regions expressing ICAM-1, obtained by using laser-capture microdissection, had increased HIF-1 and GLUT1 (P 0.05) gene expression. VEGF gene expression was more diffuse. In LPS rats, GLUT1 gene expression correlated (P 0.05) with left-ventricular contractility. In 5-h hypoxic cardiomyocytes, we found strong transient HIF-1 , weak VEGF, and greater prolonged GLUT1 gene expression. By comparison, the HIF-1 -GLUT1 geneinduction pattern was reversed in the left ventricle of LPS rats. Together, these results show that LPS induces hypoxia in the left ventricle associated with increased microvascular heterogeneity and decreased contractility. HIF-1 and GLUT1 gene induction are related to a heterogeneous ICAM-1 expression and may be cardioprotective during the onset of septic injury.
منابع مشابه
Myocardial hypoxia-inducible HIF-1alpha, VEGF, and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia.
The systemic inflammatory response to infection is the leading cause of mortality in North American intensive-care units. Although much is known about inflammatory mediators, the relationships between microregional inflammation, microvascular heterogeneity, hypoxia, hypoxia-inducible gene expression, and myocardial dysfunction are unknown. Male Sprague-Dawley rats were injected intraperitoneall...
متن کاملInvestigation of the effect of sublethal concentrations of endosulfan on gene expression of hypoxia-inducible factors (HIF-1 α and HIF-2 α) and vascular endothelial growth factor (VEGF) in the Persian sturgeon fingerlings (Acipenser persicus)
In this study, the effects of sublethal concentrations of the Endosulfan on gene expression of hypoxia-inducible factor (HIF-1 α, HIF-2 α) and vascular endothelial growth factor (VEGF) in the gill tissue of Persian sturgeon fingerling (Acipenser persicus) were studied. A total of 360 sturgeons (average weight of 2 ± 0.12 g) exposed to concentrations of 10, 20 and 40 micrograms per liter and VEG...
متن کاملThe Effect of Aerobic Training on Tumor Necrosis Factor alpha, Hypoxia-Inducible Factor-1 alpha & Vascular Endothelial Growth Factor Gene Expression in Cardiac Tissue of Diabetic Rats
Objective: The goal of this research was to determine the influence of 4 weeks aerobic training on gene expression of tumor necrosis factor alpha (TNF-α), hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in the cardiac tissue of diabetic rats. Materials and Methods: In an experimental study, 30 male wistar rats were partitioned into three groups (n=10), d...
متن کاملBlockade of Hypoxia: The Impact on Tumor Growth in an Experimental Tumor Model
Background: Tumor microenvironment is an active factor participating in immunoregulation, thereby preventing immunosurveillance and limiting the efficacy of anticancer therapies. Hypoxia as a major characteristic of solid tumors causes the expression of Hypoxia-Inducible Factor-1α (HIF-1α). This is a transcription factor that mediates hypoxic responses of tumor cells and involves in the express...
متن کاملEffect of 8 weeks of Aerobic Training on Genes Expression of Hypoxia Inducible Factor HIF-1α, Vascular Endothelial Growth Factor (VEGF) and Angiostatin in Hippocampus of Male Rats with Wistar Model
Introduction: Many studies have been done about the effects of exercise on angiogenic inhibitor and stimulator factors in muscles, but few studies have examined the role of these factors in the brain especially the hippocampus. Therefore, the purpose of the current study was to investigate the effect of 8 weeks of aerobic training on gene expression of HIF-1α, VEGF and angiostatin in hippocampu...
متن کامل