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首页 » J. Clin. Invest.:成纤维细胞在心力衰竭方面的重要作用

J. Clin. Invest.:成纤维细胞在心力衰竭方面的重要作用

来源:生命经纬 2009-12-24 13:26

成纤维细胞(Fibroblasts)是心脏中数量最多的细胞,但是在心力衰竭方面,相比于心肌细胞,科学家认为其并不是很重要。然而,日本东京大学研究生院医学研究科的科研人员一项最新研究表明,成纤维细胞在老鼠心脏对疾病,比如高血压的应答中是必不可少的。心脏如果持续高压会最终导致心力衰竭。

这项研究是由Ryozo  Nagai和  Ichiro  Manabe主持的,研究表明,心肌细胞中缺乏Klf5的老鼠对血压升高表现出正常的反应,而在成纤维细胞中缺乏Klf5的老鼠则不能对高血压表现出应答。令人惊奇的是,在成纤维细胞中缺乏Klf5的老鼠会发展成更加严重的心力衰竭,相比于正常的老鼠,并可能死于血压的过度偏高。

因此,研究人员认为,成纤维细胞在心脏应答血压变化过程中承担了重要的作用,通过调节这些细胞的功能或可以提供一种治疗心力衰竭的方法。(生物谷Bioon.com)

生物谷推荐原始出处:

J. Clin. Invest. doi:10.1172/JCI40295.

Cardiac fibroblasts are essential for the adaptive response of the murine heart to pressure overload

Norifumi Takeda1, Ichiro Manabe1,2,3, Yuichi Uchino1, Kosei Eguchi1, Sahohime Matsumoto1, Satoshi Nishimura1,3, Takayuki Shindo3,4, Motoaki Sano3,5, Kinya Otsu6, Paige Snider7, Simon J. Conway7 and Ryozo Nagai1,2,8,9

1Department of Cardiovascular Medicine and
2Global COE Program, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
3PRESTO, Japan Science and Technology Agency, Saitama, Japan.
4Department of Organ Regeneration, Shinshu University Graduate School of Medicine, Nagano, Japan.
5Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, Tokyo, Japan.
6Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
7Riley Heart Research Center, Herman B Wells Center for Pediatric Research, Indiana University of Medicine, Indianapolis, Indiana, USA.
8Comprehensive Center of Education and Research for Chemical Biology of the Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
9Translational Research Center, University of Tokyo Hospital, Tokyo, Japan.

Fibroblasts, which are the most numerous cell type in the heart, interact with cardiomyocytes in vitro and affect their function; however, they are considered to play a secondary role in cardiac hypertrophy and failure. Here we have shown that cardiac fibroblasts are essential for the protective and hypertrophic myocardial responses to pressure overload in vivo in mice. Haploinsufficiency of the transcription factor–encoding gene Krüppel-like factor 5 (Klf5) suppressed cardiac fibrosis and hypertrophy elicited by moderate-intensity pressure overload, whereas cardiomyocyte-specific Klf5 deletion did not alter the hypertrophic responses. By contrast, cardiac fibroblast–specific Klf5 deletion ameliorated cardiac hypertrophy and fibrosis, indicating that KLF5 in fibroblasts is important for the response to pressure overload and that cardiac fibroblasts are required for cardiomyocyte hypertrophy. High-intensity pressure overload caused severe heart failure and early death in mice with Klf5-null fibroblasts. KLF5 transactivated Igf1 in cardiac fibroblasts, and IGF-1 subsequently acted in a paracrine fashion to induce hypertrophic responses in cardiomyocytes. Igf1 induction was essential for cardioprotective responses, as administration of a peptide inhibitor of IGF-1 severely exacerbated heart failure induced by high-intensity pressure overload. Thus, cardiac fibroblasts play a pivotal role in the myocardial adaptive response to pressure overload, and this role is partly controlled by KLF5. Modulation of cardiac fibroblast function may provide a novel strategy for treating heart failure, with KLF5 serving as an attractive target.

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