Insulin-like growth factor-1 attenuates the detrimental impact of nonocclusive coronary artery constriction on the heart.
Coronary artery narrowing (CAN) induces tissue injury, which may involve myocyte necrosis and apoptosis. Insulin-like growth factor (IGF)-1 may counteract cell death, modifying the detrimental effects of myocardial ischemia. On this basis, CAN was produced in female FVB.Igf+/- mice and nontransgenic littermates, and the animals were euthanized 7 days later. CAN consisted of an 82% reduction in the vessel luminal cross-sectional area in both groups of mice. Severe left ventricular dysfunction was present in CAN nontransgenic and transgenic mice, but heart and left ventricular weights increased more in littermates than in FVB.Igf+/- mice. Similarly, the changes in chamber volume and diastolic wall stress were greater in nontransgenic mice. Subacute tissue injury, represented by foci of replacement fibrosis, was 2.6-fold higher in CAN littermates than in FVB.Igf+/- mice. Ongoing myocyte necrosis was 5-fold greater in nontransgenic mice, whereas apoptosis was low and did not differ in the 2 groups of mice. In CAN nontransgenic mice, myocyte necrosis was 12-fold more frequent than apoptosis but, in CAN transgenic mice, these 2 types of cell death were comparable. alpha-Myosin and beta-myosin isoform mRNAs were affected by CAN, but alpha-myosin mRNA was reduced more in nontransgenic mice. In conclusion, myocyte necrosis and replacement fibrosis are the prevailing forms of myocardial damage induced by CAN. Constitutive overexpression of IGF-1 attenuates myocyte necrosis and tissue injury, having no effect on cell apoptosis. These factors limit ventricular dilation, myocardial loading, cardiac hypertrophy, and alterations in alpha- and beta-myosin isoform expression.
D000818:Animals; D001835:Body Weight / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D003331:Coronary Vessels / Q000503:physiopathology*; D004249:DNA Damage / Q000502:physiology; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009218:Myosins / Q000235:genetics; D009929:Organ Size / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000378:metabolism / Q000473:pathology*