Induction of Haemeoxygenase-1 Directly Improves Endothelial Function in Isolated Aortas from Obese Rats through the Ampk-Pi3k/Akt-Enos Pathway

Fang Han, Ying Guo, Lili Xu, Ningning Hou, Fei Han, Xiaodong Sun
Cellular Physiology and Biochemistry 2015, 36 (4): 1480-90

BACKGROUND: Induction of haemeoxygenase-1 (HO-1) increases adiponectin secretion by remodeling adipose tissue in obesity. The objective of our study is to explore whether HO-1 induction directly improves endothelial function independent of adiponectin changes in obese rats.

METHODS: Rats were divided into control and obesity groups. Aortic endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV). Vascular segments of the obese rats were incubated in an organ bath in the presence or absence of cobalt protoporphyrin (CoPP) or CoPP plus stannous protoporphyrin. Nitric oxide (NO) production, superoxide anion production and NF-κB p65 expression in the aorta were determined. The expression of AMP-activated kinase (AMPK), Akt and endothelial nitric oxide synthase (eNOS) in endothelial cells was determined by western blotting. The aortic rings from the obese rats were then incubated with CoPP in the presence of specific inhibitors of AMPK, phosphatidylinositol 3-kinase (PI3K) or eNOS.

RESULTS: Acetylcholine-induced EDV was significantly attenuated in the obese rats, compared with the NC group (p < 0.05). Pre-incubation of vessels from obese rats with CoPP significantly increased EDV (p < 0.05). However, this beneficial effect of CoPP was partly attenuated in vitro in the presence of inhibitors of AMPK, PI3K or eNOS. HO-1 induction with CoPP significantly increased the activation of the AMPK-PI3K/Akt-eNOS pathway and NO production in parallel with reduced superoxide anion production and NF-κB p65 expression in obese rats.

CONCLUSIONS: HO-1 induction with CoPP directly improved endothelial function in obese rats independent of adiponectin changes. The mechanism of this protective effect is related to increasing NO production by activation of the AMPK-PI3K/Akt-eNOS signaling pathway.

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