衰老对心肌梗死后细胞凋亡的影响。
The effects of aging on apoptosis following myocardial infarction.
作者信息
Boyle Andrew J, Hwang Joy, Ye Jianqin, Shih Henry, Jun Kristine, Zhang Yan, Fang Qizhi, Sievers Richard, Yeghiazarians Yerem, Lee Randall J
机构信息
Department of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, CA, USA; Edyth and Eli Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
出版信息
Cardiovasc Ther. 2013 Dec;31(6):e102-10. doi: 10.1111/1755-5922.12043.
BACKGROUND
Aging is associated with higher incidence of heart failure and death following myocardial infarction (MI). The molecular and cellular changes that lead to these worse outcomes are not known.
METHODS AND RESULTS
Young and aging mice underwent induction of MI by LAD ligation. There was a significant increase in mortality in the aging mice. Neither the young nor aging hearts after MI had inducible ventricular tachycardia. Cardiomyocyte apoptosis increases early after MI in young and aging mice, but to a much greater degree in the aging mice. Caspase inhibition with Ac-DEVD-CHO resulted in a 61% reduction in activated caspase-3 and an 84% reduction in apoptosis in cardiomyocytes in young mice (P < 0.05), but not in aging mice. Gene pathway profiling demonstrated activation of both the caspase and Map3k1/Mapk10 pathways in aging mice following MI, which may contribute to their resistance to caspase inhibition.
CONCLUSIONS
Aging hearts activate distinct apoptotic pathways have more cardiomyocyte apoptosis and are resistant to antiapoptotic therapies following MI. Novel or combination approaches may be required to improve outcomes in aging patients following MI.
背景
衰老与心肌梗死（MI）后心力衰竭和死亡的发生率较高相关。导致这些更差结果的分子和细胞变化尚不清楚。
方法与结果
对年轻和衰老小鼠进行左前降支（LAD）结扎诱导心肌梗死。衰老小鼠的死亡率显著增加。心肌梗死后，年轻和衰老小鼠的心脏均未出现可诱导的室性心动过速。心肌梗死后早期，年轻和衰老小鼠的心肌细胞凋亡均增加，但衰老小鼠的凋亡程度要大得多。用Ac-DEVD-CHO抑制半胱天冬酶导致年轻小鼠心肌细胞中活化的半胱天冬酶-3减少61%，凋亡减少84%（P<0.05），但衰老小鼠无此效果。基因通路分析表明，心肌梗死后衰老小鼠的半胱天冬酶和Map3k1/Mapk10通路均被激活，这可能导致它们对半胱天冬酶抑制产生抗性。
结论
衰老心脏激活不同的凋亡途径，有更多的心肌细胞凋亡，并且在心肌梗死后对抗凋亡治疗有抗性。可能需要新的或联合的方法来改善老年心肌梗死患者的预后。
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