Clinical impact of myocardial mTORC1 activation in nonischemic dilated cardiomyopathy
2016
Abstract Background Activity of mTOR complex 1 (
mTORC1) has been shown to be up-regulated in animal models of heart failure. Here, we investigated the change and role of
mTORC1in human nonischemic
dilated cardiomyopathy(NICM). Methods Endomyocardial biopsy specimens were obtained from patients with NICM (n = 52) and from
Brugada syndromepatients with normal LVEF as controls (n = 10). The specimens were stained for phospho-
ribosomal protein S6(p-Rps6) and phospho-p70S6K (p-p70S6K), and the area with p-Rps6 signal was used as an index of
mTORC1activity. Using median
mTORC1activity, patients were divided into a high
mTORC1activity (H-mTOR) group and a low
mTORC1activity (L-mTOR) group. Results The ratio of p-Rps6-positive area in biopsy samples was 10-fold larger in patients with NICM than in controls (2.0 ± 2.2% vs. 0.2 ± 0.2%, p P = 0.10). Conclusion Aberrant activation of
mTORC1in cardiomyocytes was associated with myocardial fibrosis and a trend for worse prognosis in patients with NICM, indicating that persistently activated
mTORC1contributes to progression of human heart failure.
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