FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction

Engel  FB; Hsieh  PCH; Lee  RTKeating  MT

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FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction

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Mammalian cardiomyocytes have limited proliferation potential, and acutely injured mammalian hearts do not regenerate adequately. Instead, injured myocardium develops fibrosis and scarring. Here we show that FGF1/p38 MAP kinase inhibitor treatment after acute myocardial injury in 8- to 10-week-old rats increases cardiomyocyte mitosis. At 3 months after injury, 4 weeks of FGF1/p38 MAP kinase inhibitor therapy results in reduced scarring and wall thinning, with markedly improved cardiac function. In contrast, p38 MAP kinase inhibition alone fails to rescue heart function despite increased cardiomyocyte mitosis. FGF1 improves angiogenesis, possibly contributing to the survival of newly generated cardiomyocytes. Our data indicate that FGF1 and p38 MAP kinase, proteins involved in cardiomyocyte proliferation and angiogenesis during development, may be delivered therapeutically to enhance cardiac regeneration.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2006年第42期|15546-15551|共6页
作者
Engel FB; Hsieh PCH; Lee RTKeating MT;
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作者单位

Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA;

Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA;

Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USANovartis Inst Biomed Res, Cambridge, MA 02139 USA;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
cardiac regeneration; fractional shortening; cyclin D2; cyclin A; angiogenesis; FIBROBLAST-GROWTH-FACTOR; ASSEMBLING PEPTIDE NANOFIBERS; CYCLIN-DEPENDENT KINASES; CARDIAC STEM-CELLS; TRANSGENIC MICE; DNA-SYNTHESIS; HEART; ANGIOGENESIS; REGENERATION; ISCHEMIA;

FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction

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