BIOPSY-PROVEN ACTIVE MYOCARDITIS IN SYSTEMIC SCLEROSIS PATIENTS WITH RECENT-ONSET CARDIAC INVOLVEMENT

Abstract

superoxide production (lucigenin chemiluminescence) and expression levels of cardiac autophagic markers and signaling proteins (Western blot) and hypertrophic genes (real time-PCR) were analyzed. Fructose-fed mice exhibited normal plasma insulin, but were glucose intolerant and hyperglycaemic. In the absence of obesityand hypertension-induced loading influences, elevated superoxide production (fructose, 553± 28 counts/s/mg vs. control, 489± 11 counts/s/mg, p< 0.05) and suppression of the PI3K/Akt cell survival pathway (decreased pAkt:Akt and pS6:S6 protein expression ratio) were observed in hearts of fructose-fed mice. Fructose feeding induced cardiac autophagy activation (LC3B-II:LC3B-I protein expression ratio, 46%increase), suggestiveofmyocyte loss. The high fructose diet decreased gene expression of cardiacgrowthmarkers ( -MHC:71%decrease,p< 0.05; BNP: 58% decrease, p< 0.05) despite no change in whole heart weight. The present study demonstrates that insulin resistance and hyperglycemia is associated with suppressed myocardial cell survival signaling and activated cardiac autophagy.Thesefindingshave important implications for the characterization of diabetic cardiomyopathy and further work is required to elucidate the precisemechanisms involved. doi:10.1016/j.hlc.2010.06.759