Interaction of BMP10 with Tcap may modulate the course of hypertensive cardiac hypertrophy.
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.
Nakano
Noritsugu
N
Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Hori
Hisae
H
Abe
Minako
M
Shibata
Hiroki
H
Arimura
Takuro
T
Sasaoka
Taishi
T
Sawabe
Motoji
M
Chida
Kouji
K
Arai
Tomio
T
Nakahara
Ken-ichi
K
Kubo
Toru
T
Sugimoto
Ken
K
Katsuya
Tomohiro
T
Ogihara
Toshio
T
Doi
Yoshinori
Y
Izumi
Tohru
T
Kimura
Akinori
A
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
D019485:Bone Morphogenetic Proteins; D064211:Connectin; D017077:Culture Media, Conditioned; D009124:Muscle Proteins; D017673:Sodium Chloride, Dietary; C577292:TCAP protein, human