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首页> 外文期刊>Endocrinology >Adrenomedullin-RAMP2 and-RAMP3 Systems Regulate Cardiac Homeostasis during Cardiovascular Stress
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Adrenomedullin-RAMP2 and-RAMP3 Systems Regulate Cardiac Homeostasis during Cardiovascular Stress

机译:adrenomedullin-ramp2和-ramp3系统在心血管压力期间调节心脏稳态

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摘要

Adrenomedullin (AM) is a peptide hormone with multiple physiological functions, which are regulated by its receptor activity-modifying proteins, RAMP2 and RAMP3. We previously reported that AM or RAMP2 knockout (KO) (AM-/-, RAMP2-/-) is embryonically lethal in mice, whereas RAMP3-/- mice are apparently normal. AM, RAMP2, and RAMP3 are all highly expressed in the heart; however, their functions there are not fully understood. Here, we analyzed the pathophysiological functions of the AM-RAMP2 and AM-RAMP3 systems in hearts subjected to cardiovascular stress. Cardiomyocyte-specific RAMP2-/- (C-RAMP2-/-) and RAMP3-/- showed no apparent heart failure at base line. After 1 week of transverse aortic constriction (TAC), however, C-RAMP2-/- exhibited significant cardiac hypertrophy, decreased ejection fraction, and increased fibrosis compared with wild-type mice. Both dP/dtmax and dP/dtmin were significantly reduced in C-RAMP2-/-, indicating reduced ventricular contractility and relaxation. Exposing C-RAMP2-/- cardiomyocytes to isoproterenol enhanced their hypertrophy and oxidative stress compared with wild-type cells. C-RAMP2-/- cardiomyocytes also contained fewer viable mitochondria and showed reduced mitochondria! membrane potential and respiratory capacity. RAMP3-/- also showed reduced systolic function and enhanced fibrosis after TAC, but those only became apparent after 4 weeks. A reduction in cardiac lymphatic vessels was the characteristic feature in RAMP3-/-. These observations indicate the AM-RAMP2 system is necessary for early adaptation to cardiovascular stress through regulation of cardiac mitochondria. AM-RAMP3 is necessary for later adaptation through regulation of lymphatic vessels. The AM-RAMP2 and AM-RAMP3 systems thus play separate critical roles in the maintenance of cardiovascular homeostasis against cardiovascular stress.
机译:None

著录项

  • 来源
    《Endocrinology》 |2021年第3期|共20页
  • 作者单位

    Shinshu Univ Dept Cardiovasc Res Sch Med Asahi 3-1-1 Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Cardiovasc Res Sch Med Asahi 3-1-1 Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Cardiovasc Res Sch Med Asahi 3-1-1 Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Cardiovasc Res Sch Med Asahi 3-1-1 Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Cardiovasc Res Sch Med Asahi 3-1-1 Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Cardiovasc Res Sch Med Asahi 3-1-1 Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Cardiovasc Res Sch Med Asahi 3-1-1 Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Cardiovasc Res Sch Med Asahi 3-1-1 Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Cardiovasc Res Sch Med Asahi 3-1-1 Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Cardiovasc Res Sch Med Asahi 3-1-1 Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Cardiovasc Res Sch Med Asahi 3-1-1 Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Mol Pharmacol Sch Med Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Res Ctr Supports Adv Sci Dept Instrumental Anal Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Mol Pharmacol Sch Med Matsumoto Nagano 3908621 Japan;

    Shinshu Univ Dept Cardiovasc Res Sch Med Asahi 3-1-1 Matsumoto Nagano 3908621 Japan;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
  • 关键词

    adrenomedullin; heart failure; cardiac hypertrophy; cardiac fibrosis; mitochondria; lymphatic vessel;

    机译:肾上腺细胞素;心力衰竭;心脏肥大;心肌纤维化;线粒体;淋巴血管;

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