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Myocardial Vascular Protection in Hibernating Woodchucks
Author(s) -
Zhang Jie,
Vatner Dorothy E.,
Guers John,
Vatner Stephen F
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.845.3
Subject(s) - hibernation (computing) , medicine , hibernating myocardium , cardiology , arteriogenesis , myocardial infarction , endocrinology , ischemia , revascularization , state (computer science) , algorithm , computer science
True mammalian hibernation is a remarkable and natural mechanism to change the body's metabolism to meet the ravages of winter, when the animals do not eat or drink. At one point it was thought that these protective mechanisms related only to metabolism of fat and muscle including thermogenic protection. The goal of this study was to elucidate how the novel mechanisms elicited in hibernation can protect the heart from myocardial ischemia in an animal model with no coronary artery disease. Accordingly we compared the effects of myocardial infarction (MI) induced by permanent coronary artery occlusion (CAO) for 2 months in woodchucks in summer, when they were not hibernating, and in winter when they were. During hibernation they were markedly protected, p<0.05, from myocardial ischemia with reduced infarct size (37± 2.3% in winter, vs 47±3.1% in summer) and mortality (14% in winter vs 52% in summer) and preserved cardiac function as assessed by left ventricular ejection fraction (58±3.3% in winter, vs 42±3.3% in summer). The only way this might be possible in the face of permanent CAO would be if angiogenesis/arteriogenesis developed in the hibernating hearts following CAO. Indeed this is what was observed and determined by Ki67 + endothelial cell staining (0.60± 0.13% in winter vs 0.09±0.02% in summer). We then identified the vascular growth factors (VEGF, cTGF, PDGF, and EGR1) that were upregulated in the hibernating woodchuck heart, including nitric oxide synthase and CREB. Thus, natural mammalian hibernation induces marked cardioprotection through induction of angiogenesis/arteriogenesis. Support or Funding Information This study was supported by NIH funding R01HL130848.