title: Ryanodine receptor type 2 is required for the development of pressure overload-induced cardiac hypertrophy.
abstract: Ryanodine receptor type 2 (RyR-2) mediates Ca(2+) release from sarcoplasmic reticulum and contributes to myocardial contractile function. However, the role of RyR-2 in the development of cardiac hypertrophy is not completely understood. Here, mice with or without reduction of RyR-2 gene (RyR-2(+/-) and wild-type, respectively) were analyzed. At baseline, there was no difference in morphology of cardiomyocyte and heart and cardiac contractility between RyR-2(+/-) and wild-type mice, although Ca(2+) release from sarcoplasmic reticulum was impaired in isolated RyR-2(+/-) cardiomyocytes. During a 3-week period of pressure overload, which was induced by constriction of transverse aorta, isolated RyR-2(+/-) cardiomyocytes displayed more reduction of Ca(2+) transient amplitude, rate of an increase in intracellular Ca(2+) concentration during systole, and percentile of fractional shortening, and hearts of RyR-2(+/-) mice displayed less compensated hypertrophy, fibrosis, and contractility; more apoptosis with less autophagy of cardiomyocytes; and similar decrease of angiogenesis as compared with wild-type ones. Moreover, constriction of transverse aorta-induced increases in the activation of calcineurin, extracellular signal-regulated protein kinases, and protein kinase B/Akt but not that of Ca(2+)/calmodulin-dependent protein kinase II, and its downstream targets in the heart of wild-type mice were abolished in the RyR-2(+/-) one, suggesting that RyR-2 is a regulator of calcineurin, extracellular signal-regulated protein kinases, and Akt but not of calmodulin-dependent protein kinase II activation during pressure overload. Taken together, our data indicate that RyR-2 contributes to the development of cardiac hypertrophy and adaptation of cardiac function during pressure overload through regulation of the sarcoplasmic reticulum Ca(2+) release; activation of calcineurin, extracellular signal-regulated protein kinases, and Akt; and cardiomyocyte survival.
authors: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Rd, Shanghai 200032, China. zou.yunzeng@zs-hospital.sh.cn
authors: Yunzeng
authors: Y
authors: Zou
authors: Yanyan
authors: Y
authors: Liang
authors: Hui
authors: H
authors: Gong
authors: Ning
authors: N
authors: Zhou
authors: Hong
authors: H
authors: Ma
authors: Aili
authors: A
authors: Guan
authors: Aijun
authors: A
authors: Sun
authors: Ping
authors: P
authors: Wang
authors: Yuhong
authors: Y
authors: Niu
authors: Hong
authors: H
authors: Jiang
authors: Hiroyuki
authors: H
authors: Takano
authors: Haruhiro
authors: H
authors: Toko
authors: Atsushi
authors: A
authors: Yao
authors: Hiroshi
authors: H
authors: Takeshima
authors: Hiroshi
authors: H
authors: Akazawa
authors: Ichiro
authors: I
authors: Shiojima
authors: Yuqi
authors: Y
authors: Wang
authors: Issei
authors: I
authors: Komuro
authors: Junbo
authors: J
authors: Ge
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D019703:Calcineurin / Q000378:metabolism; D020013:Calcium Signaling; D048429:Cell Size; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020869:Gene Expression Profiling; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D011312:Pressure / Q000009:adverse effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014463:Ultrasonography
chemical_list: D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D019703:Calcineurin