Relationship between effect of PPARγ in pulmonary vascular remodeling and NOX-4 in rats with pulmonary hypertension

Abstract

Objective To evaluate the relationship between the effect of peroxisome proliferator-activated receptor-γ (PPARγ) in pulmonary vascular remodeling and NADPH oxidase 4 (NOX-4) in rats with pulmonary hypertension. Methods Thirty-two healthy adult male Sprague-Dawley rats, aged 2 months, weighing 200-250 g, were divided into 4 groups(n=8 each)using a random number table method: control group (group C), pulmonary arterial hypertension group (group PH), PPARγ agonist rosiglitazone treatment group (group R), and PPARγ antagonist GW9662 treatment group (group G). In group PH, monocrotaline 60 mg/kg was injected subcutaneously in the neck and back to induce pulmonary hypertension.The suspension of rosiglitazone and normal saline 5 mg·kg-1·d-1 and GW9662 solution 2 mg·kg-1·d-1 were administered by intragastric gavage after injecting monocrotaline, in group R and group G, respectively, for 4 consecutive weeks.The mean pulmonary arterial pressure (mPAP) was measured at 4 weeks after establishing the model.The animals were then sacrificed, and the lungs were removed for microscopic examination of the pathological changes (with a light microscope) and for determination of the expression of PPARγ and NOX-4 protein and mRNA in lung tissues(by real-time polymerase chain reaction or Western blot). The percentage of media thickness of pulmonary arterioles was calculated. Results Compared with group C, the mPAP and percentage of media thickness of pulmonary arterioles were significantly increased, the expression of PPARγ protein and mRNA was down-regulated, and the expression of NOX-4 protein and mRNA was up-regulated in PH, R and G groups (P<0.05). Compared with group PH, the mPAP and percentage of media thickness of pulmonary arterioles were significantly decreased, the expression of PPARγ protein and mRNA was up-regulated, and the expression of NOX-4 protein and mRNA was down-regulated in group R, and the mPAP and percentage of media thickness of pulmonary arterioles were significantly increased, the expression of PPARγ protein and mRNA was down-regulated, and the expression of NOX-4 protein and mRNA was up-regulated in group G (P<0.05). Conclusion The mechanism of endogenous protective effect of PPARγ in the development of pulmonary hypertension and pulmonary vascular remodeling may be related to down-regulating the expression of NOX-4 in rats. Key words: PPAR gamma; Hypertension, pulmonary; Pulmonary artery; Cell proliferation; NADPH oxidase