title: Interaction of BMP10 with Tcap may modulate the course of hypertensive cardiac hypertrophy.
abstract: 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.
authors.affiliation: Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Noritsugu
authors.initials: N
authors.lastname: Nakano
authors.forename: Hisae
authors.initials: H
authors.lastname: Hori
authors.forename: Minako
authors.initials: M
authors.lastname: Abe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shibata
authors.forename: Takuro
authors.initials: T
authors.lastname: Arimura
authors.forename: Taishi
authors.initials: T
authors.lastname: Sasaoka
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
authors.forename: Kouji
authors.initials: K
authors.lastname: Chida
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nakahara
authors.forename: Toru
authors.initials: T
authors.lastname: Kubo
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Doi
authors.forename: Tohru
authors.initials: T
authors.lastname: Izumi
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019898:Autocrine Communication; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D048429:Cell Size; D002478:Cells, Cultured; D064211:Connectin; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational; D011485:Protein Binding; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D019485:Bone Morphogenetic Proteins; D064211:Connectin; D017077:Culture Media, Conditioned; D009124:Muscle Proteins; D017673:Sodium Chloride, Dietary; C577292:TCAP protein, human