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This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/H3396    most recent 00311.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nakano, N. Articles by Kimura, A. Search for Related Content PubMed PubMed Citation Articles by Nakano, N. Articles by Kimura, A.

Interaction of BMP10 with Tcap may modulate the course of hypertensive cardiac hypertrophy

¹Department of Molecular Pathogenesis, Medical Research Institute, and ²Laboratory of Genome Diversity, School of Biomedical Science, Tokyo Medical and Dental University, Tokyo; ³Department of Internal Medicine and Cardiology, Kitasato University School of Medicine, Kanagawa; ⁴Tokyo Metropolitan Geriatric Hospital, Tokyo; ⁵Nagasaki Medical Center, National Hospital Organization, Nagasaki; ⁶Department of Medicine and Geriatrics, Kochi University School of Medicine, Kochi; and ⁷Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

Submitted 13 March 2007 ; accepted in final form 11 September 2007

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.

bone morphogenetic protein-10; wall stress; Z disc; cardiomyopathy