Abstract:
:As described in earlier reviews in this series on the molecular basis of hypertrophic cardiomyopathy (HCM), HCM is one of the archetypal monogenic cardiovascular disorders to be understood at the molecular level. Twenty years after the discovery of the first HCM disease gene, genetic studies still confirm that HCM is principally a disease of the sarcomere. At the biophysical level, myofilament mutations generally enhance Ca(2+) sensitivity, maximal force production, and ATPase activity. These defects ultimately appear to converge on energy deficiency and altered Ca(2+) handling as major common paths leading to the anatomic (hypertrophy, myofiber disarray, and fibrosis) and functional features (pathological signaling and diastolic dysfunction) characteristic of HCM. In this review, we provide an account of the consequences of HCM mutations and describe how specifically targeting these molecular features has already yielded early promise for novel therapies for HCM. Although substantial efforts are still required to understand the molecular link between HCM mutations and their clinical consequences, HCM endures as an exemplar of how novel insights derived from molecular characterization of Mendelian disorders can inform the understanding of biological processes and translate into rational therapies.
journal_name
Circ Resjournal_title
Circulation researchauthors
Ashrafian H,McKenna WJ,Watkins Hdoi
10.1161/CIRCRESAHA.111.242974subject
Has Abstractpub_date
2011-06-24 00:00:00pages
86-96issue
1eissn
0009-7330issn
1524-4571pii
109/1/86journal_volume
109pub_type
杂志文章,评审abstract::Power ratios were derived from the principle of ultrasonic Doppler velocimetry to determine a ratio of the volume of vortices to the total vessel volume under the ultrasonic beam. This ratio also equals the ratio of the cross-sectional area of vortices to the vessel lumen. In vitro pulsatile flow experiments were perf...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.1.166
更新日期:1990-07-01 00:00:00
abstract::Brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are novel natriuretic peptides, originally isolated from porcine brain. Similar to atrial natriuretic peptide (ANP), BNP is also synthesized in and secreted from cardiocytes, but CNP is not expressed at significant levels in normal adult myocardium. ...
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pub_type: 杂志文章
doi:10.1161/01.res.71.1.9
更新日期:1992-07-01 00:00:00
abstract::Previous studies have demonstrated a role for voltage-gated K+ (Kv) channel alpha subunits of the Kv4 subfamily in the generation of rapidly inactivating/recovering cardiac transient outward K+ current, I(to,f), channels. Biochemical studies suggest that mouse ventricular I(to,f) channels reflect the heteromeric assem...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000196559.63223.aa
更新日期:2005-12-09 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.118.311378
更新日期:2018-09-14 00:00:00
abstract::In nonischemic heart failure (HF), ventricular tachycardia initiates by a nonreentrant mechanism, but there is altered conduction (that could lead to re-entry) that could arise from changes in gap junctional proteins, especially connexin43 (Cx43). We studied Cx43 expression and phosphorylation state in the left ventri...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000152325.07495.5a
更新日期:2005-01-07 00:00:00
abstract:RATIONALE:We have shown recently that particulate (pGC) and soluble guanylyl (sGC) cyclases synthesize cGMP in different compartments in adult rat ventricular myocytes (ARVMs). OBJECTIVE:We hypothesized that cGMP-dependent protein kinase (PKG) exerts a feedback control on cGMP concentration contributing to its intrace...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.226712
更新日期:2010-11-12 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.305421
更新日期:2015-05-22 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.310933
更新日期:2017-08-18 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.43.2.293
更新日期:1978-08-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.4.918
更新日期:1991-10-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000171451.88616.c2
更新日期:2005-06-24 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.307647
更新日期:2016-04-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1993-12-01 00:00:00
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doi:10.1161/CIRCRESAHA.116.309301
更新日期:2016-12-09 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.275586
更新日期:2013-01-04 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000268412.34364.50
更新日期:2007-05-25 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2001.097691
更新日期:2001-10-12 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.311049
更新日期:2017-05-12 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1976-05-01 00:00:00
abstract::When exposed to an increasing transmural pressure, middle cerebral arteries of the cat exhibit reduction of internal diameter which is mediated by vascular muscle cell depolarization. This laboratory has recently demonstrated that this "pressure-induced" activation is dependent upon the presence of an intact endotheli...
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pub_type: 杂志文章
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更新日期:1989-07-01 00:00:00
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更新日期:1998-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:2007-08-17 00:00:00
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journal_title:Circulation research
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更新日期:2007-07-20 00:00:00
abstract::Age-related diastolic dysfunction is a major factor in the epidemic of heart failure. In patients hospitalized with heart failure, HFpEF is now as common as heart failure with reduced ejection fraction. We now have many successful treatments for heart failure with reduced ejection fraction, while specific treatment op...
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pub_type: 杂志文章,评审
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更新日期:2014-06-20 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.86.10.1093
更新日期:2000-05-26 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.314202
更新日期:2019-07-05 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.314438
更新日期:2019-04-12 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1976-05-01 00:00:00
abstract::The aim of the study was to investigate whether the adrenal renin-angiotensin system plays an independent role in the regulation of mineralocorticoid biosynthesis in the adrenal gland and to explore the mechanisms of this action. Twelve-week-old male Sprague-Dawley rats were studied: 22 rats were maintained on a regul...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.5.857
更新日期:1997-11-01 00:00:00
abstract::The consequences of endothelin receptor activation were examined in atrial tumor myocytes derived from transgenic mice (AT-1 cells). Endothelin-1 (endothelin) stimulates phosphoinositide hydrolysis in a dose-dependent manner. Endothelin also induces the rapid and transient translocation of protein kinase C (PKC)-epsil...
journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1996-04-01 00:00:00