机构：[1]Division of Cardiology and Cardiovascular Research Institute, University of California, 505 Parnassus Avenue, M1182, Box 0124, San Francisco, CA 94143, USA[2]Arrhythmia Center, Guangdong Provincial Hospital of Traditional Chinese Medicine, China广东省中医院[3]UCSF SABRE Center Microarray Core Facility, University of California, San Francisco, CA, USA
Animal studies show that transforming growth factor-1 (TGF-1) is an important mediator of atrial fibrosis and atrial fibrillation (AF). This study investigated the role of TGF-1 in human AF and the mechanism of atrial-selective fibrosis. Atrial specimens from 17 open heart surgery patients and left atrial and ventricular specimens from 17 explanted hearts were collected to assess the relationship between TGF-1, AF, and differential atrial vs. ventricular TGF-1 levels. A transgenic mouse model overexpressing active TGF-1 was used to study the mechanisms underlying the resultant atrial-selective fibrosis. Higher right atrial total TGF-1 levels (2.58 0.16-fold, P 0.0001) and active TGF-1 (3.7 0.7-fold, P 0.013) were observed in those that developed post-operative AF. Although no ventricular differences were observed, 11 explanted heart failure hearts exhibited higher atrial TGF-1 levels than 6 non-failing hearts (2.30 0.87 fold higher, P 0.001). In the transgenic mouse, TGF-1 receptor-1 kinase blockade resulted in decreased atrial expression of fibrosis-related genes. By RNA microarray analyses in that model, 80 genes in the atria and only 2 genes in the ventricle were differentially expressed. Although these mice atria, but not the ventricles, exhibited increased expression of fibrosis-related genes and phosphorylation of Smad2, there were no differences in TGF-1 receptor levels or Smads in the atria compared with the ventricles. TGF-1 mediates selective atrial fibrosis in AF that occurs via TGF- Receptor 1/2 and the classical Smad pathway. The differential atrial vs. ventricular fibrotic response occurs at the level of TGF-1 receptor binding or phosphorylation.
基金：
This work was supported by NIH (grant RO1-HL072854 to J.E.O.,
RC1-HL099789 to J.E.O.), and the Stephen and Nancy Grand Fund. G.M.M. was supported by the NIH (NCRR, KL2 RR024130), a component
of the NIH, and the Joseph Drown Foundation. Microarray experiments
were performed at the UCSF SABRE Center with the support of
the NIH/NCRR UCSF-CTSI (grant number UL1 RR024131).
第一作者机构：[1]Division of Cardiology and Cardiovascular Research Institute, University of California, 505 Parnassus Avenue, M1182, Box 0124, San Francisco, CA 94143, USA
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通讯作者：
推荐引用方式(GB/T 7714)：
Dolkun Rahmutula,Gregory M. Marcus,Emily E. Wilson,et al.Molecular basis of selective atrial fibrosis due to overexpression of transforming growth factor-1[J].CARDIOVASCULAR RESEARCH.2013,99(4):769-779.doi:10.1093/cvr/cvt074.
APA：
Dolkun Rahmutula,Gregory M. Marcus,Emily E. Wilson,Chun-Hua Ding,Yuanyuan Xiao...&Jeffrey E. Olgin.(2013).Molecular basis of selective atrial fibrosis due to overexpression of transforming growth factor-1.CARDIOVASCULAR RESEARCH,99,(4)
MLA：
Dolkun Rahmutula,et al."Molecular basis of selective atrial fibrosis due to overexpression of transforming growth factor-1".CARDIOVASCULAR RESEARCH 99..4(2013):769-779
医学