Understanding cardiomyopathy phenotypes based on the functional impact of mutations in the myosin motor.

Abstract:

:Hypertrophic (HCM) and dilated (DCM) cardiomyopathies are inherited diseases with a high incidence of death due to electric abnormalities or outflow tract obstruction. In many of the families afflicted with either disease, causative mutations have been identified in various sarcomeric proteins. In this review, we focus on mutations in the cardiac muscle molecular motor, myosin, and its associated light chains. Despite the >300 identified mutations, there is still no clear understanding of how these mutations within the same myosin molecule can lead to the dramatically different clinical phenotypes associated with HCM and DCM. Localizing mutations within myosin's molecular structure provides insight into the potential consequence of these perturbations to key functional domains of the motor. Review of biochemical and biophysical data that characterize the functional capacities of these mutant myosins suggests that mutant myosins with enhanced contractility lead to HCM, whereas those displaying reduced contractility lead to DCM. With gain and loss of function potentially being the primary consequence of a specific mutation, how these functional changes trigger the hypertrophic response and lead to the distinct HCM and DCM phenotypes will be the future investigative challenge.

journal_name

Circ Res

journal_title

Circulation research

authors

Moore JR,Leinwand L,Warshaw DM

doi

10.1161/CIRCRESAHA.110.223842

subject

Has Abstract

pub_date

2012-07-20 00:00:00

pages

375-85

issue

3

eissn

0009-7330

issn

1524-4571

pii

111/3/375

journal_volume

111

pub_type

杂志文章,评审
  • Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease.

    abstract:RATIONALE:Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. OBJECTIVE:To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressur...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.116.304846

    authors: Varbo A,Benn M,Smith GD,Timpson NJ,Tybjaerg-Hansen A,Nordestgaard BG

    更新日期:2015-02-13 00:00:00

  • Peroxisome proliferator-activated receptor alpha induces NADPH oxidase activity in macrophages, leading to the generation of LDL with PPAR-alpha activation properties.

    abstract::Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors controlling lipid and glucose metabolism as well as inflammation. PPARs are expressed in macrophages, cells that also generate reactive oxygen species (ROS). In this study, we investigated whether PPARs regulate ROS production in macrophages. Di...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000150594.95988.45

    authors: Teissier E,Nohara A,Chinetti G,Paumelle R,Cariou B,Fruchart JC,Brandes RP,Shah A,Staels B

    更新日期:2004-12-10 00:00:00

  • Decline in Cardiovascular Mortality: Possible Causes and Implications.

    abstract::If the control of infectious diseases was the public health success story of the first half of the 20th century, then the decline in mortality from coronary heart disease and stroke has been the success story of the century's past 4 decades. The early phase of this decline in coronary heart disease and stroke was unex...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.116.309115

    authors: Mensah GA,Wei GS,Sorlie PD,Fine LJ,Rosenberg Y,Kaufmann PG,Mussolino ME,Hsu LL,Addou E,Engelgau MM,Gordon D

    更新日期:2017-01-20 00:00:00

  • Acetylcholine-sensitive intracellular Ca2+ store in fresh endothelial cells and evidence for ryanodine receptors.

    abstract::In a freshly isolated endothelial cell preparation from rabbit aorta, the regulation of the acetylcholine (ACh)-sensitive intracellular Ca2+ store and the effects of the Ca(2+)-induced Ca2+ release agonists ryanodine and caffeine were studied using fura 2 imaging fluorescence microscopy. ACh (10 mumol/L) caused a tran...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.77.1.37

    authors: Wang X,Lau F,Li L,Yoshikawa A,van Breemen C

    更新日期:1995-07-01 00:00:00

  • Revisiting Cardiac Cellular Composition.

    abstract:RATIONALE:Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and regeneration. OBJECTIVE:To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells, and ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.115.307778

    authors: Pinto AR,Ilinykh A,Ivey MJ,Kuwabara JT,D'Antoni ML,Debuque R,Chandran A,Wang L,Arora K,Rosenthal NA,Tallquist MD

    更新日期:2016-02-05 00:00:00

  • Coupling of Fcγ receptor I to Fcγ receptor IIb by SRC kinase mediates C-reactive protein impairment of endothelial function.

    abstract:RATIONALE:Elevations in C-reactive protein (CRP) are associated with increased cardiovascular disease risk and endothelial dysfunction. CRP antagonizes endothelial nitric oxide synthase (eNOS) through processes mediated by the IgG receptor Fcγ receptor IIB (FcγRIIB), its immunoreceptor tyrosine-based inhibitory motif, ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.111.254573

    authors: Sundgren NC,Zhu W,Yuhanna IS,Chambliss KL,Ahmed M,Tanigaki K,Umetani M,Mineo C,Shaul PW

    更新日期:2011-10-28 00:00:00

  • Activated RhoA stimulates c-fos gene expression in myocardial cells.

    abstract::Rho regulates various cell functions, including cell morphology and motility. However, the functional role of Rho on the signaling pathway in myocardial cells (MCs) is unknown. In the present study, we attempted to explore the mode of Rho action for c-fos gene expression in MCs. Expression of the c-fos promoter/enhanc...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.81.5.672

    authors: Ueyama T,Sakoda T,Kawashima S,Hiraoka E,Hirata K,Akita H,Yokoyama M

    更新日期:1997-11-01 00:00:00

  • Fetal blood volume responses to acute fetal hemorrhage.

    abstract::The purpose of this study was to explore the changes in fetal blood volume that occur after fetal hemorrhage. Fifteen unanesthetized, chronically catheterized fetal sheep averaging 130 +/- 3 (SD) days gestation were studied 4 to 6 (average 5) days after catheter implantation. The fetuses were hemorrhaged by continuous...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.52.6.730

    authors: Brace RA

    更新日期:1983-06-01 00:00:00

  • Direct neurohumoral evidence for isolated sympathetic nervous system activation to skeletal muscle in response to cardiopulmonary baroreceptor unloading.

    abstract::It has been postulated that cardiopulmonary baroreceptor unloading in humans results in nonuniform activation of the sympathetic nervous system. We reasoned that simultaneous measurements of arterial and venous norepinephrine (NE) spillover and clearance (using NE kinetics), muscle sympathetic neural activity (using m...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.66.6.1720

    authors: Baily RG,Prophet SA,Shenberger JS,Zelis R,Sinoway LI

    更新日期:1990-06-01 00:00:00

  • In vivo estimation of cardiac transmembrane current.

    abstract::The ionic currents that cross the myocardial membrane during cardiac activation have a corresponding return path in the extracellular space. The transmembrane current (Im) during activation of cardiac cells in situ has previously been envisioned only in mathematical models. We have developed a remarkably simple in viv...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.72.2.424

    authors: Witkowski FX,Kavanagh KM,Penkoske PA,Plonsey R

    更新日期:1993-02-01 00:00:00

  • Signal transduction in atria and ventricles of mice with transient cardiac expression of activated G protein alpha(q).

    abstract::We recently showed that the transient expression of a hemagglutinin (HA) epitope-tagged, constitutively active mutant of the G protein alpha(q) subunit (HAalpha(q)*) in the hearts of transgenic mice is sufficient to induce cardiac hypertrophy and dilatation that continue to progress after HAalpha(q)* protein becomes u...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.85.11.1085

    authors: Mende U,Kagen A,Meister M,Neer EJ

    更新日期:1999-11-26 00:00:00

  • Sustained inward current during pacemaker depolarization in mammalian sinoatrial node cells.

    abstract::Several time- and voltage-dependent ionic currents have been identified in cardiac pacemaker cells, including Na(+) current, L- and T-type Ca(2+) currents, hyperpolarization-activated cation current, and various types of delayed rectifier K(+) currents. Mathematical models have demonstrated that spontaneous action pot...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.res.87.2.88

    authors: Mitsuiye T,Shinagawa Y,Noma A

    更新日期:2000-07-21 00:00:00

  • Novel Risk Markers and Risk Assessments for Cardiovascular Disease.

    abstract::The use of risk markers has transformed cardiovascular medicine, exemplified by the routine assessment of troponin, for both diagnosis and assessment of prognosis in patients with chest pain. Clinical risk factors form the basis for risk assessment of cardiovascular disease and the addition of biochemical, cellular, a...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.116.309955

    authors: Thomas MR,Lip GY

    更新日期:2017-01-06 00:00:00

  • Distinct receptors and signaling pathways in alpha-thrombin- and thrombin receptor peptide-induced vascular contractions.

    abstract::The vasoactive mechanisms of the serine protease alpha-thrombin were examined in isolated coronary arteries from dogs. In resting coronary arteries with endothelium, alpha-thrombin caused concentration-dependent contractions that were characterized by an initial transient relaxation followed by slowly developing susta...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.74.5.930

    authors: Tesfamariam B

    更新日期:1994-05-01 00:00:00

  • Heat shock protein 90alpha-dependent translocation of annexin II to the surface of endothelial cells modulates plasmin activity in the diabetic rat aorta.

    abstract::The goals of this article were (1) to identify cell surface proteins whose expression was regulated by diabetes and (2) to assess their contribution to diabetic complications. We purified heat shock protein 90alpha (Hsp90alpha) from the membrane fraction of high glucose-treated endothelial cells (ECs) as a binding par...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000124979.46214.E3

    authors: Lei H,Romeo G,Kazlauskas A

    更新日期:2004-04-16 00:00:00

  • Modulation of Ca2+ channels by cyclic nucleotide cross activation of opposing protein kinases in rabbit portal vein.

    abstract::Cyclic nucleotides are known to modify voltage-gated (L-type) Ca2+ channel activity in vascular smooth muscle cells, but the exact mechanism(s) underlying these effects is not well defined. The purpose of the present study was to investigate the modulatory role of the cAMP- and cGMP-dependent protein kinase (PKA and P...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.82.5.557

    authors: Ruiz-Velasco V,Zhong J,Hume JR,Keef KD

    更新日期:1998-03-23 00:00:00

  • Direct effect of beta-adrenergic stimulation on renin release by the rat kidney slice in vitro.

    abstract::Controversy exists regarding the mechanism by which catecholamines stimulate renin secretion in vivo. A sensitive rat kidney slice system was utilized to study the direct effects of adrenergic agonists and antagonists on renin release in vitro. Catecholamines were protected from degradation by the addition of ascorbic...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.37.3.318

    authors: Weinberger MH,Aoi W,Henry DP

    更新日期:1975-09-01 00:00:00

  • High-Density Lipoprotein Carries Markers That Track With Recovery From Stroke.

    abstract:RATIONALE:Prospective cohort studies question the value of HDL-C (high-density lipoprotein cholesterol) for stroke risk prediction. OBJECTIVE:Investigate the relationship between long-term functional recovery and HDL proteome and function. METHODS AND RESULTS:Changes in HDL protein composition and function (cholester...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.120.316526

    authors: Plubell DL,Fenton AM,Rosario S,Bergstrom P,Wilmarth PA,Clark WM,Zakai NA,Quinn JF,Minnier J,Alkayed NJ,Fazio S,Pamir N

    更新日期:2020-10-23 00:00:00

  • Short-term exercise training enhances reflex cholinergic nitric oxide-dependent coronary vasodilation in conscious dogs.

    abstract::The effects of exercise training on the coronary vasodilation following activation of the Bezold-Jarisch reflex were examined in conscious dogs. Mongrel dogs were chronically instrumented using sterile techniques for measurements of systemic hemodynamics and left circumflex coronary blood flow (CBF). With the heart ra...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.80.6.868

    authors: Zhao G,Zhang X,Xu X,Ochoa M,Hintze TH

    更新日期:1997-06-01 00:00:00

  • Phosphorylation and adenosine triphosphatase activity of myofibrils from thyrotoxic rabbit hearts.

    abstract::Cardiac hypertrophy induced by thyrotoxic stress leads to an increase in the rate of force development, velocity of shortening, tension-dependent heat generation, and myosin ATPase activity. We did studies to see whether alterations in covalent phosphorylation of myofibrillar proteins correlate with these changes. The...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.48.4.498

    authors: Litten RZ 3rd,Martin BJ,Howe ER,Alpert NR,Solaro RJ

    更新日期:1981-04-01 00:00:00

  • Cellular bioenergetics is an important determinant of the molecular imaging signal derived from luciferase and the sodium-iodide symporter.

    abstract:RATIONALE:Molecular imaging is useful for longitudinal assessment of engraftment. However, it is not known which factors, other than cell number, can influence the molecular imaging signal obtained from reporter genes. OBJECTIVE:The effects of cell dissociation/suspension on cellular bioenergetics and the signal obtai...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.112.273375

    authors: Chang C,Chan A,Lin X,Higuchi T,Terrovitis J,Afzal JM,Rittenbach A,Sun D,Vakrou S,Woldemichael K,O'Rourke B,Wahl R,Pomper M,Tsui B,Abraham MR

    更新日期:2013-02-01 00:00:00

  • Phorbol diester modulates alpha-adrenergic receptor-coupled calcium efflux and alpha-adrenergic receptor number in cultured vascular smooth muscle cells.

    abstract::The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate was used to probe the role of protein kinase-C in the modulation of alpha-adrenergic receptor-coupled calcium efflux in cultured vascular smooth muscle cells derived from rabbit aorta. Exposure of cells to 12-O-tetradecanoyl phorbol-13-acetate for 6 minutes cause...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.58.3.393

    authors: Colucci WS,Gimbrone MA Jr,Alexander RW

    更新日期:1986-03-01 00:00:00

  • Mechanisms of supersensitivity to sympathomimetic amines in the chronically denervated heart of the conscious dog.

    abstract::Mechanisms of denervation supersensitivity to sympathomimetic amines were studied in conscious animals. Norepinephrine, 0.1 micrograms/kg, increased left ventricular dP/dt significantly more (4208 +/- 828 mm Hg/sec) in dogs with cardiac denervation than in intact dogs (1029 +/- 280 mm Hg/sec), P less than 0.01, wherea...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.57.1.55

    authors: Vatner DE,Lavallee M,Amano J,Finizola A,Homcy CJ,Vatner SF

    更新日期:1985-07-01 00:00:00

  • Effects of quinapril, a new angiotensin converting enzyme inhibitor, on left ventricular failure and survival in the cardiomyopathic hamster. Hemodynamic, morphological, and biochemical correlates.

    abstract::The effect of chronic therapy with quinapril on the temporal progression of left ventricular failure and survival was assessed in the CHF 146 cardiomyopathic (CM) hamster, which is an idiopathic model of congestive heart failure. Age-matched Golden Syrian (GS) hamsters served as normal controls. Quinapril was administ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.5.1302

    authors: Haleen SJ,Weishaar RE,Overhiser RW,Bousley RF,Keiser JA,Rapundalo SR,Taylor DG

    更新日期:1991-05-01 00:00:00

  • From Loci to Biology: Functional Genomics of Genome-Wide Association for Coronary Disease.

    abstract::Genome-wide association studies have provided a rich collection of ≈ 58 coronary artery disease (CAD) loci that suggest the existence of previously unsuspected new biology relevant to atherosclerosis. However, these studies only identify genomic loci associated with CAD, and many questions remain even after a genomic ...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.115.306464

    authors: Nurnberg ST,Zhang H,Hand NJ,Bauer RC,Saleheen D,Reilly MP,Rader DJ

    更新日期:2016-02-19 00:00:00

  • MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and vascular remodeling in vivo.

    abstract:RATIONALE:MicroRNA (miR)-1 and -133 play a crucial role in skeletal and cardiac muscle biology and pathophysiology. However, their expression and regulation in vascular cell physiology and disease is currently unknown. OBJECTIVE:The aim of the present study was to evaluate the role, if any, of miR-1 and miR-133 in vas...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.111.240150

    authors: Torella D,Iaconetti C,Catalucci D,Ellison GM,Leone A,Waring CD,Bochicchio A,Vicinanza C,Aquila I,Curcio A,Condorelli G,Indolfi C

    更新日期:2011-09-30 00:00:00

  • Vascular remodeling and improvement of coronary reserve after hydralazine treatment in spontaneously hypertensive rats.

    abstract::The purpose of these studies was to evaluate cardiovascular structural and functional changes in a model of hypertension-induced myocardial hypertrophy in which vasodilator therapy decreased blood pressure to normal levels. Thus, we determined the separate contributions of hypertension and hypertrophy on myocardial an...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.64.6.1127

    authors: Anderson PG,Bishop SP,Digerness SB

    更新日期:1989-06-01 00:00:00

  • MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation.

    abstract::MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate about 30% of the encoding genes of the human genome. However, the role of miRNAs in vascular disease is currently completely unknown. Using microarray analysis, we demonstrated for the first time that miRNAs are aberr...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.106.141986

    authors: Ji R,Cheng Y,Yue J,Yang J,Liu X,Chen H,Dean DB,Zhang C

    更新日期:2007-06-08 00:00:00

  • Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog.

    abstract::In 57 normal subjects (age 20-60 years), we analyzed the spontaneous beat-to-beat oscillation in R-R interval during control recumbent position, 90 degrees upright tilt, controlled respiration (n = 16) and acute (n = 10) and chronic (n = 12) beta-adrenergic receptor blockade. Automatic computer analysis provided the a...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.59.2.178

    authors: Pagani M,Lombardi F,Guzzetti S,Rimoldi O,Furlan R,Pizzinelli P,Sandrone G,Malfatto G,Dell'Orto S,Piccaluga E

    更新日期:1986-08-01 00:00:00

  • The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase.

    abstract::Trimetazidine is a clinically effective antianginal agent that has no negative inotropic or vasodilator properties. Although it is thought to have direct cytoprotective actions on the myocardium, the mechanism(s) by which this occurs is as yet undefined. In this study, we determined what effects trimetazidine has on b...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.86.5.580

    authors: Kantor PF,Lucien A,Kozak R,Lopaschuk GD

    更新日期:2000-03-17 00:00:00