Effects of PPARβand NO on high glucose and insulin-induced cardio-myocyte hypertrophy / 中国病理生理杂志

ABSTRACT

AIM:To investigate the role of peroxisome proliferator-activated receptor β( PPARβ)-nitric oxide (NO) signal pathway in cardiomyocyte hypertrophy induced by high glucose (25.5 mmol/L) and insulin (0.1 μmol/L) ( HGI) .METHODS: The cardiomyocyte hypertrophy was characterized in rat primary cardiomyocytes by measuring the cell surface area, protein content, and the mRNA expression of atrial natriuretic factor (ANF).The mRNA and protein ex-pression were measured by real-time PCR and Western blotting , respectively .The activity of NO synthase ( NOS) and NO content were measured by a reagent kit through ultraviolet spectroscopy .RESULTS:HGI induced profound change of hy-pertrophic morphology , and significantly increased the cell surface area , protein content and mRNA expression of ANF (P<0.01), but decreased the expression of PPARβat mRNA and protein levels (P<0.05).At the same time, the ex-pression of inducible NOS (iNOS) was obviously elevated (P<0.01), which occurred in parallel with the rising NOS ac-tivity and NO concentration (P<0.01).GW0742 (1 μmol/L), a selective PPARβagonist, inhibited the cardiomyocyte hypertrophy induced by HGI ( P<0.01 ) , and up-regulated the expression of PPARβat both mRNA and protein levels . Meanwhile, GW0742 also inhibited the increases in iNOS expression , NOS activity, and NO content induced by HGI , which were abolished by GSK0660 (1 μmol/L), a selective PPARβantagonist (P<0.01).CONCLUSION: PPARβdown-regulation and the following iNOS-NO activation are involved in the cardiomyocyte hypertrophy induced by HGI .