Obesity increases transcription of heme oxygenase-1 gene and synergistically stimulates angiogenesis with vascular endothelial growth factor and plasminogen activator inhibitor-1 in rats

ABSTRACT

Angiogenesis plays an important role in obesity; heme oxygenase-1 [HO-1] has been implicated in the process of angiogenesis. To investigate the effect of obesity on transcription of HO-1 gene and to study the relation between elevated HO-1 and other angiogenic factors such as vascular endothelial growth factor [VEGF] and plasminogen activator inhibitor -1 [PAI-1] which are though to play an important role in the pathogenesis of obesity. Obesity was induced in 15 albino rats by feeding high fat diet for 3 months to establish diet-induced obesity. Another 15 rats were used as control. Blood samples were collected from tail vein; plasma PAI-1, lipid profile, free fatty acids [FFA], leptin and VEGF were measured. RNA was extracted from liver of obese and normal rats and RT-PCR was done, beta-actin mRNA expression for each sample was used as internal control. In rats fed high fat diets for 3 months, the total body weight were significantly increased [247.0 +/- 14.66g] compared to control group [126.37 +/- 23.26 g]. Obese rats showed a significant increase in serum triacylglycerol [TAC], total cholesterol [TC], low density lipoproteins-cholesterol [LDL-C], leptin and plasma free fatty acids, while serum high-density lipoproteins-cholesterol [HDL-C] was significantly decreased. HO-1-mRNA was increased in liver homogenates of obese rats compared to non-obese rats. These results indicate that the body response to obesity by elevating the expression of the stress gene HO-I. Angiogenic factors VEGF and PAI-I were significantly increased in obese compared to non-obese rats. Our findings suggest that HO-I and angiogenic factors [VEGF and PAI-I] play an important role in pathogenesis of obesity