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Autophagy, metabolic syndrome, and heart surgery
Author(s) -
Mentzer Robert M,
Jahania Salik M,
Sengstock David,
Vaitkevicius Peter,
Andres Allen,
Ito Bruce R,
Gottlieb Roberta A
Publication year - 2013
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.27.1_supplement.449.2
Subject(s) - autophagy , cardiac surgery , medicine , downregulation and upregulation , atg5 , cardiopulmonary bypass , cardioprotection , cardiology , surgery , biology , ischemia , apoptosis , biochemistry , gene
Myocardial stress has been linked to induction of autophagy. Rodent and porcine models of metabolic syndrome exhibit impaired autophagy and may explain loss of cardioprotection. To test the hypothesis that cardiac stress is associated with upregulation of autophagy in humans, autophagic flux was measured in 12 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Right atrial tissue (200–400 mg) was excised during atrial cannulation, before initiation of CPB and aortic cross‐clamping, and again after removal of cross‐clamp and weaning from CPB. Autophagy proteins Beclin‐1, Atg5–12, and p62 were analyzed by Western blot. Heart surgery was associated with significant decreases in cardiac levels of Beclin‐1, Atg5–12, and p62, indicating robust autophagic flux. The magnitude of change was correlated with calculated mortality/morbidity (M/M) risk scores extracted from patient medical records using the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database. There was a significant inverse relationship between the change in p62 and risk score. This is the first time that upregulation of autophagic flux has been linked to better outcomes after heart surgery. Strategies designed to upregulate flux during conditions of cardiac stress may have therapeutic utility and represent a new approach to patients with ischemic heart disease and metabolic syndrome in which autophagy is impaired. Grant Funding Source: supported by an NIH Grant (NIH 2 R01 HL034579–23 and 5R01 AG033283)