Document Detail

Interaction of BMP10 with Tcap may modulate the course of hypertensive cardiac hypertrophy.
MedLine Citation:
PMID:  17921333     Owner:  NLM     Status:  MEDLINE    
Elevated wall stress by hypertension induces an adaptive myocardial hypertrophy via releasing prohypertrophic hormones such as angiotensin II. In this study, we investigated the involvement of bone morphogenetic protein-10 (BMP10) in hypertension-induced cardiac hypertrophy. Expression of BMP10 was increased in the hypertrophied ventricles from hypertensive rats. BMP10 localized on cell surface and at stretch-sensing Z disc of cardiomyocytes, where BMP10 interacted with a protein called titin-cap (Tcap). A rare variant of the human BMP10 gene, Thr326Ile, was found to be associated with hypertensive dilated cardiomyopathy. The variant BMP10 demonstrated decreased binding to Tcap and increased extracellular secretion. Conditioned medium from cells transfected with wild-type or variant BMP10 induced hypertrophy in rat neonatal cardiomyocytes, except that medium from variant BMP10-carrying cells showed an enhanced effect reflecting the increased secretion. These observations suggested that hypertension induced expression of prohypertrophic BMP10, and the hypertrophic effect of BMP10 was modulated, at least in part, by its binding to Tcap at the Z disc.
Noritsugu Nakano; Hisae Hori; Minako Abe; Hiroki Shibata; Takuro Arimura; Taishi Sasaoka; Motoji Sawabe; Kouji Chida; Tomio Arai; Ken-ichi Nakahara; Toru Kubo; Ken Sugimoto; Tomohiro Katsuya; Toshio Ogihara; Yoshinori Doi; Tohru Izumi; Akinori Kimura
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-05
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  293     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-12-06     Completed Date:  2008-01-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H3396-403     Citation Subset:  IM    
Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
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MeSH Terms
Animals, Newborn
Autocrine Communication*
Bone Morphogenetic Proteins / genetics,  metabolism*
Cardiomegaly / etiology,  metabolism*,  pathology
Cell Size
Cells, Cultured
Culture Media, Conditioned / metabolism
Disease Models, Animal
Disease Progression
Hypertension / complications*,  etiology,  metabolism,  pathology
Muscle Proteins / genetics,  metabolism*
Myocytes, Cardiac / metabolism*,  pathology
Polymorphism, Single-Stranded Conformational
Protein Binding
Rats, Inbred SHR
Rats, Sprague-Dawley
Sodium Chloride, Dietary
Time Factors
Reg. No./Substance:
0/Bone Morphogenetic Proteins; 0/Culture Media, Conditioned; 0/Muscle Proteins; 0/Sodium Chloride, Dietary; 0/TCAP protein, human

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