Myocardial hypoxia-inducible HIF-1alpha, VEGF, and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia.
Am J Physiol Heart Circ Physiol
; 293(1): H448-56, 2007 Jul.
Article
em En
| MEDLINE
| ID: mdl-17369472
ABSTRACT
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 three-dimensional microvascular imaging, tissue Po(2), 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 hypoxia-inducible genes hypoxia-inducible factor (HIF)-1alpha, 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-1alpha 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-1alpha, weak VEGF, and greater prolonged GLUT1 gene expression. By comparison, the HIF-1alpha-GLUT1 gene-induction 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-1alpha and GLUT1 gene induction are related to a heterogeneous ICAM-1 expression and may be cardioprotective during the onset of septic injury.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Molécula 1 de Adesão Intercelular
/
Endotoxemia
/
Fator A de Crescimento do Endotélio Vascular
/
Transportador de Glucose Tipo 1
/
Subunidade alfa do Fator 1 Induzível por Hipóxia
/
Microcirculação
/
Miocárdio
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Heart Circ Physiol
Assunto da revista:
CARDIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Canadá