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Sestrins (Sesns) were originally identified as critical antioxidant proteins and involved in complex regulation of cell viability in response to diverse stress conditions. The present study aimed to examine the heart expression and function of Sesns in ischemic cardiomyopathy patients and ischemia stressed mice.
Left ventricular tissues from end-stage heart failure (HF) patients with ischemic cardiomyopathy and unmatched donors were collected to detect the expression and function of Sesns by real-time PCR, western Blotting and immunofluorescence staining. Mice myocardial ischemia/reperfusion (I/R) and myocardial infarction (MI) models were established to confirm the expression of Sesns.
All members of Sesns (Sesn1, Sesn2 and Sesn3) were expressed in the extracellular matrix of human hearts. No difference was found for the expression of Sesn1 or Sesn3 between failing and control hearts. Surprisingly, Sesn2 was significantly up-regulated in human failing hearts (mRNA levels: 1.63±0.28 vs 1.00±0.18, p＜0.05). Furthermore, double immunofluorescence staining revealed that Sesn2 was co-expressed with vimentin, a marker for fibroblasts. Correlation analysis demonstrated Sesn2 levels were significantly correlated with expression levels of natriuretic peptide B (NPPB) and connective tissue growth factor (CTGF) (r=0.542, p＜0.05; r=0.561, p＜0.05, respectively), markers for severity of HF and cardiac fibrosis. The increased expression of Sesn2 was validated in mice I/R and MI models. More importantly, Sesn2 mRNA levels were significantly higher in 4 weeks MI hearts than that in 1 week MI hearts (5.17±0.53 vs 2.19±0.13, p＜0.01).
Sesn2 was increased in human and mice ischemic hearts and might involve in cardiac fibrosis through regulating the function of fibroblasts.