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Telomerase deficiency predisposes to heart failure and ischemia‐reperfusion Injury
Author(s) -
AitAissa Karima,
Heisner James S,
Strande Jennifer L,
Harmann Leanne,
Camara Amadou K.S.,
Beyer Andreas M
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.845.5
Subject(s) - medicine , cardiology , ischemia , heart failure , myocardial infarction , cardiac function curve , coronary artery disease , diastole , infarction , reperfusion injury , blood pressure
Coronary heart disease remains one of the main cause of death worldwide. With lack of successful treatment, new therapeutic targets and effective treatments are yet to be discovered. Hypothesis Our preliminary results suggest a strong correlation between telomerase impairment and impaired mitochondrial respiration in hearts from human subjects with coronary artery disease. Additionally, it has been shown that acute overexpression of the catalytic subunit of telomerase, TERT, increases survival rate and decreases infarct size in left anterior descending artery ligation mice model. In the present study, we examined the role of TERT on cardiac structure and function under baseline conditions and following ischemic stress. Methods Transthoracic echocardiogram was performed on wild‐type (WT) and TERT knockout rats (TERT −/− ) to assess cardiac structure and function. To evaluate heart function further, Langendorf model was used to evaluate the effects of acute global ischemia reperfusion (I/R) on cardiac function and infarction. Coronary Flow (CF) and left ventricular pressure (LVP) were measured continuously online before, during and after 30 min no flow global ischemia. Functional data were assessed at 60 min reperfusion while infarct sizes were determined at the end of the 120 min reperfusion using TTC staining. Results Echocardiographic analysis revealed early singes of diastolic heart failure in TERT −/− rats. No change in CF or LVP was found during pre‐ischemia, however, at 60 min reperfusion); infarct size was reduced in TERT −/− rats (TERT −/− : 36±2%*; WT: 42±1%; n=7–8; *p<0.05). Functionally TERT −/− had decreased recovery as Isovolumic relaxation time was decreased (TERT −/− : 11.36±0.74ms*; WT: 13.9±0.59ms; n=12; *p<0.05) while E velocity was elevated more in TERT −/− (TERT −/− :1.15±0.03ms*; WT: 1.02±0.04ms; n=12; *p<0.05) suggesting a component of diastolic dysfunction in the setting of increased intracardiac pressures. Conclusion TERT deficiency causes additional cardiac dysfunction unrelated to the degree of myocardial necrosis suggesting underlying metabolic defects in TERT −/− rats. These results suggest a therapeutic role of telomerase to prevent heart failure after myocardial infarction.