The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Yuji Matsumoto - One of the best experts on this subject based on the ideXlab platform.
-
functional analysis of titin connectin n2 b mutations found in Cardiomyopathy
Journal of Muscle Research and Cell Motility, 2006Co-Authors: Yuji Matsumoto, Takeharu Hayashi, Natsuko Inagaki, Megumi Takahashi, Shitoshi Hiroi, Takeyuki Nakamura, Takuro Arimura, Kazufumi Nakamura, Naoto AshizawaAbstract:Hypertrophic Cardiomyopathy and dilated Cardiomyopathy are two major clinical phenotypes of “idiopathic” Cardiomyopathy. Recent molecular genetic analyses have now revealed that “idiopathic” Cardiomyopathy is caused by mutations in genes for sarcomere components. We have recently reported several mutations in titin/connectin gene found in patients with hypertrophic Cardiomyopathy or dilated Cardiomyopathy. A hypertrophic Cardiomyopathy-associated titin/connectin mutation (Arg740Leu) was found to increase the binding to actinin, while other dilated Cardiomyopathy-associated titin/connectin mutations (Ala743Val and Val54Met) decreased the binding to actinin and Tcap/telethonin, respectively. We also reported several other mutations in the N2-B region of titin/connectin found in hypertrophic Cardiomyopathy and dilated Cardiomyopathy. Since the N2-B region expresses only in the heart, it was speculated that functional alterations due to the mutations cause cardiomyopathies. In this study, we investigated the functional changes caused by the N2-B region mutations by using yeast-two-hybrid assays. It was revealed that a hypertrophic Cardiomyopathy-associated mutation (Ser3799Tyr) increased the binding to FHL2 protein, whereas a dilated Cardiomyopathy-associated mutation (Gln4053ter) decreased the binding. In addition, another TTN mutation (Arg25618Gln) at the is2 region was found in familial DCM. Because FHL2 protein is known to tether metabolic enzymes to N2-B and is2 regions of titin/connectin, these observations suggest that altered recruitment of metabolic enzymes to the sarcomere may play a role in the pathogenesis of cardiomyopathies.
-
Functional analysis of titin/connectin N2-B mutations found in Cardiomyopathy
Journal of Muscle Research & Cell Motility, 2005Co-Authors: Yuji Matsumoto, Takeharu Hayashi, Natsuko Inagaki, Megumi Takahashi, Shitoshi Hiroi, Takeyuki Nakamura, Takuro Arimura, Kazufumi Nakamura, Naoto Ashizawa, Michio YasunamiAbstract:Hypertrophic Cardiomyopathy and dilated Cardiomyopathy are two major clinical phenotypes of “idiopathic” Cardiomyopathy. Recent molecular genetic analyses have now revealed that “idiopathic” Cardiomyopathy is caused by mutations in genes for sarcomere components. We have recently reported several mutations in titin/connectin gene found in patients with hypertrophic Cardiomyopathy or dilated Cardiomyopathy. A hypertrophic Cardiomyopathy-associated titin/connectin mutation (Arg740Leu) was found to increase the binding to actinin, while other dilated Cardiomyopathy-associated titin/connectin mutations (Ala743Val and Val54Met) decreased the binding to actinin and Tcap/telethonin, respectively. We also reported several other mutations in the N2-B region of titin/connectin found in hypertrophic Cardiomyopathy and dilated Cardiomyopathy. Since the N2-B region expresses only in the heart, it was speculated that functional alterations due to the mutations cause cardiomyopathies. In this study, we investigated the functional changes caused by the N2-B region mutations by using yeast-two-hybrid assays. It was revealed that a hypertrophic Cardiomyopathy-associated mutation (Ser3799Tyr) increased the binding to FHL2 protein, whereas a dilated Cardiomyopathy-associated mutation (Gln4053ter) decreased the binding. In addition, another TTN mutation (Arg25618Gln) at the is2 region was found in familial DCM. Because FHL2 protein is known to tether metabolic enzymes to N2-B and is2 regions of titin/connectin, these observations suggest that altered recruitment of metabolic enzymes to the sarcomere may play a role in the pathogenesis of cardiomyopathies.
Naoto Ashizawa - One of the best experts on this subject based on the ideXlab platform.
-
functional analysis of titin connectin n2 b mutations found in Cardiomyopathy
Journal of Muscle Research and Cell Motility, 2006Co-Authors: Yuji Matsumoto, Takeharu Hayashi, Natsuko Inagaki, Megumi Takahashi, Shitoshi Hiroi, Takeyuki Nakamura, Takuro Arimura, Kazufumi Nakamura, Naoto AshizawaAbstract:Hypertrophic Cardiomyopathy and dilated Cardiomyopathy are two major clinical phenotypes of “idiopathic” Cardiomyopathy. Recent molecular genetic analyses have now revealed that “idiopathic” Cardiomyopathy is caused by mutations in genes for sarcomere components. We have recently reported several mutations in titin/connectin gene found in patients with hypertrophic Cardiomyopathy or dilated Cardiomyopathy. A hypertrophic Cardiomyopathy-associated titin/connectin mutation (Arg740Leu) was found to increase the binding to actinin, while other dilated Cardiomyopathy-associated titin/connectin mutations (Ala743Val and Val54Met) decreased the binding to actinin and Tcap/telethonin, respectively. We also reported several other mutations in the N2-B region of titin/connectin found in hypertrophic Cardiomyopathy and dilated Cardiomyopathy. Since the N2-B region expresses only in the heart, it was speculated that functional alterations due to the mutations cause cardiomyopathies. In this study, we investigated the functional changes caused by the N2-B region mutations by using yeast-two-hybrid assays. It was revealed that a hypertrophic Cardiomyopathy-associated mutation (Ser3799Tyr) increased the binding to FHL2 protein, whereas a dilated Cardiomyopathy-associated mutation (Gln4053ter) decreased the binding. In addition, another TTN mutation (Arg25618Gln) at the is2 region was found in familial DCM. Because FHL2 protein is known to tether metabolic enzymes to N2-B and is2 regions of titin/connectin, these observations suggest that altered recruitment of metabolic enzymes to the sarcomere may play a role in the pathogenesis of cardiomyopathies.
-
Functional analysis of titin/connectin N2-B mutations found in Cardiomyopathy
Journal of Muscle Research & Cell Motility, 2005Co-Authors: Yuji Matsumoto, Takeharu Hayashi, Natsuko Inagaki, Megumi Takahashi, Shitoshi Hiroi, Takeyuki Nakamura, Takuro Arimura, Kazufumi Nakamura, Naoto Ashizawa, Michio YasunamiAbstract:Hypertrophic Cardiomyopathy and dilated Cardiomyopathy are two major clinical phenotypes of “idiopathic” Cardiomyopathy. Recent molecular genetic analyses have now revealed that “idiopathic” Cardiomyopathy is caused by mutations in genes for sarcomere components. We have recently reported several mutations in titin/connectin gene found in patients with hypertrophic Cardiomyopathy or dilated Cardiomyopathy. A hypertrophic Cardiomyopathy-associated titin/connectin mutation (Arg740Leu) was found to increase the binding to actinin, while other dilated Cardiomyopathy-associated titin/connectin mutations (Ala743Val and Val54Met) decreased the binding to actinin and Tcap/telethonin, respectively. We also reported several other mutations in the N2-B region of titin/connectin found in hypertrophic Cardiomyopathy and dilated Cardiomyopathy. Since the N2-B region expresses only in the heart, it was speculated that functional alterations due to the mutations cause cardiomyopathies. In this study, we investigated the functional changes caused by the N2-B region mutations by using yeast-two-hybrid assays. It was revealed that a hypertrophic Cardiomyopathy-associated mutation (Ser3799Tyr) increased the binding to FHL2 protein, whereas a dilated Cardiomyopathy-associated mutation (Gln4053ter) decreased the binding. In addition, another TTN mutation (Arg25618Gln) at the is2 region was found in familial DCM. Because FHL2 protein is known to tether metabolic enzymes to N2-B and is2 regions of titin/connectin, these observations suggest that altered recruitment of metabolic enzymes to the sarcomere may play a role in the pathogenesis of cardiomyopathies.
Naser Imran - One of the best experts on this subject based on the ideXlab platform.
-
Stress Cardiomyopathy (Takotsubo Cardiomyopathy)
Clinical medicine. Cardiology, 2009Co-Authors: Samer Khouri, Naser ImranAbstract:Background: Due to the rise in the number of reports of stress Cardiomyopathy in the literature, awareness of this condition is increasing. Although different names have been used to describe this condition, the similarities in clinical, electrocardiographic, echocardiographic, and angiographic features suggest that they represent the same spectrum of diseases with different underlying causes. The pathophysiology of stress Cardiomyopathy remains controversial. Methods: We describe a series of four cases of stress Cardiomyopathy admitted to our institution over a period of six months with different presentations, but similar clinical course, EKG, echocardiographic, and catheterization findings. The ages ranged from 22 to 81 years; all four females. All showed characteristic wall motion abnormalities by imaging in the absence of significant coronary artery disease, with spontaneous recovery of left ventricular function with conservative therapy. Results: Although the patients presented with different clinical scenarios, all four showed characteristic features of stress Cardiomyopathy suggesting that the pathophysiology affecting the myocardium was the same. We present a review of the literature with a discussion of the history of this condition, characteristic clinical features, and diagnostic criteria used in the past as well as the suggested pathophysiology of this condition. Conclusion: Stress Cardiomyopathy is an underdiagnosed reversible Cardiomyopathy triggered by severe emotional or physical stress. It represents a spectrum of conditions with reversible severe left ventricular systolic dysfunction that includes neurogenic Cardiomyopathy. It is not confined to the Japanese population and can affect people of any ethnic background or nationality.
Josef Finsterer - One of the best experts on this subject based on the ideXlab platform.
-
Cardiomyopathy in neurological disorders.
Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology, 2013Co-Authors: Josef Finsterer, Claudia Stollberger, Karim WahbiAbstract:According to the American Heart Association, cardiomyopathies are classified as primary (solely or predominantly confined to heart muscle), secondary (those showing pathological myocardial involvement as part of a neuromuscular disorder) and those in which Cardiomyopathy is the first/predominant manifestation of a neuromuscular disorder. Cardiomyopathies may be further classified as hypertrophic Cardiomyopathy, dilated Cardiomyopathy, restrictive Cardiomyopathy, arrhythmogenic right ventricular Cardiomyopathy, or unclassified Cardiomyopathy (noncompaction, Takotsubo-Cardiomyopathy). This review focuses on secondary cardiomyopathies and those in which Cardiomyopathy is the predominant manifestation of a myopathy. Any of them may cause neurological disease, and any of them may be a manifestation of a neurological disorder. Neurological disease most frequently caused by cardiomyopathies is ischemic stroke, followed by transitory ischemic attack, syncope, or vertigo. Neurological disease, which most frequently manifests with cardiomyopathies are the neuromuscular disorders. Most commonly associated with cardiomyopathies are muscular dystrophies, myofibrillar myopathies, congenital myopathies and metabolic myopathies. Management of neurological disease caused by cardiomyopathies is not at variance from the same neurological disorders due to other causes. Management of secondary cardiomyopathies is not different from that of cardiomyopathies due to other causes either. Patients with neuromuscular disorders require early cardiologic investigations and close follow-ups, patients with cardiomyopathies require neurological investigation and avoidance of muscle toxic medication if a neuromuscular disorder is diagnosed. Which patients with Cardiomyopathy profit most from primary stroke prevention is unsolved and requires further investigations.
-
seizure associated takotsubo Cardiomyopathy
Epilepsia, 2011Co-Authors: Claudia Stollberger, Christian Wegner, Josef FinstererAbstract:Takotsubo Cardiomyopathy is characterized by chest pain, dyspnea, electrocardiographic changes resembling an acute coronary syndrome, and transient wall-motion abnormalities without identifiable coronary culprit lesion explaining the wall-motion abnormality. Takotsubo Cardiomyopathy occurs frequently after emotional or physical stress. Seizures have been reported as triggers of takotsubo Cardiomyopathy. It is unknown if seizure-associated takotsubo Cardiomyopathy differs from takotsubo Cardiomyopathy associated with other triggers. Seizure-associated takotsubo Cardiomyopathy cases from the literature were compared with takotsubo Cardiomyopathy series comprising 30 or more patients. Thirty-six seizure-associated takotsubo Cardiomyopathy cases (6 male, mean-age 61.5 years) were found. Seizure-type were tonic-clonic (n = 13), generalized (n = 5), status epilepticus (n = 6), grand mal (n = 2), or not reported (n = 13). Twelve patients had a history of epilepsy, in 15 patients takotsubo Cardiomyopathy-associated seizure was the first or the information was not given (n = 9). In 17 patients takotsubo Cardiomyopathy occurred immediately after the seizure, in 9 patients 1-72 h postictally, and in 10 patients, the interval was not reported. In 20 patients neurologic disorders were reported and in 14 psychiatric disorders were reported. There were medical comorbidities in 17 patients, arterial hypertension (n = 11), hyponatremia (n = 2), and cancer (n = 2). Compared with 974 patients reported in takotsubo Cardiomyopathy -series, patients with seizure-associated takotsubo Cardiomyopathy were younger (61.5 vs. 68.5 years, p < 0.0001), more frequently males (17 vs. 9%, p = 0.004), had less frequent chest pain (6 vs.76%, p < 0.005), more frequent cardiogenic shock (25 vs. 8%, p = 0.003), and more frequent recurrency (14 vs. 3%, p = 0.004). Seizure-associated takotsubo Cardiomyopathy manifests frequently as sudden hemodynamic deterioration, which could result in death in the absence of adequate help. Probably some cases of sudden unexpected death in epilepsy are attributable to takotsubo Cardiomyopathy.
Akinori Kimura - One of the best experts on this subject based on the ideXlab platform.
-
Molecular genetics and pathogenesis of Cardiomyopathy
Journal of Human Genetics, 2016Co-Authors: Akinori KimuraAbstract:Cardiomyopathy is defined as a disease of functional impairment in the cardiac muscle and its etiology includes both extrinsic and intrinsic factors. Cardiomyopathy caused by the intrinsic factors is called as primary Cardiomyopathy of which two major clinical phenotypes are hypertrophic Cardiomyopathy (HCM) and dilated Cardiomyopathy (DCM). Genetic approaches have revealed the disease genes for hereditary primary Cardiomyopathy and functional studies have demonstrated that characteristic functional alterations induced by the disease-associated mutations are closely related to the clinical types, such that increased and decreased Ca^2+ sensitivities of muscle contraction are associated with HCM and DCM, respectively. In addition, recent studies have suggested that mutations in the Z-disc components found in HCM and DCM may result in increased and decreased stiffness of sarcomere, respectively. Moreover, functional analysis of mutations in the other components of cardiac muscle have suggested that the altered response to metabolic stresses is associated with Cardiomyopathy, further indicating the heterogeneity in the etiology and pathogenesis of Cardiomyopathy.
-
Cardiomyopathy, Sarcomeropathy, and Z-diskopathy
Genes and Cardiovascular Function, 2011Co-Authors: Akinori KimuraAbstract:Cardiomyopathy is caused by functional abnormalities of cardiac muscle, which include both extrinsic and intrinsic factors. The intrinsic factor involves mutations in genes playing roles in performance, regulation, or maintenance of cardiac function. Cardiomyopathy caused by the intrinsic factor is called idiopathic or primary Cardiomyopathy, and there are several clinical types of primary Cardiomyopathy including hypertrophic Cardiomyopathy and dilated Cardiomyopathy. Linkage studies and candidate gene approaches have deciphered the disease genes for hereditary primary Cardiomyopathy: mutations in genes for components of sarcomere, sarcolemma, Z-disk, proteins of I band region, nuclear membrane, and transcriptional machinery. The most interesting findings are that mutations in different disease genes can be found in the same clinical types of Cardiomyopathy and that mutations in the same disease gene can be found in different clinical types of Cardiomyopathy. Functional analyses of disease-related mutations have revealed that characteristic functional alterations are associated with each clinical type of Cardiomyopathy. In this review I focus on the Cardiomyopathy-associated mutations found in genes for sarcomere and Z-disk elements and their functional relevance in the pathogenesis of primary Cardiomyopathy.
-
Molecular basis of hereditary Cardiomyopathy: abnormalities in calcium sensitivity, stretch response, stress response and beyond
Journal of Human Genetics, 2010Co-Authors: Akinori KimuraAbstract:Cardiomyopathy is caused by functional abnormality of cardiac muscle. The functional abnormality involved in its etiology includes both extrinsic and intrinsic factors, and Cardiomyopathy caused by the intrinsic factors is called as idiopathic or primary Cardiomyopathy. There are several clinical types of primary Cardiomyopathy including hypertrophic Cardiomyopathy (HCM) and dilated Cardiomyopathy (DCM). Linkage studies and candidate gene approaches have explored the disease genes for hereditary primary Cardiomyopathy. The most notable finding was that mutations in the same disease gene can be found in different clinical types of Cardiomyopathy. Functional analyses of disease-related mutations have revealed that characteristic functional alterations are associated with the clinical types, such that increased and decreased Ca^2+ sensitivity due to sarcomere mutations are associated with HCM and DCM, respectively. In addition, our recent studies have suggested that mutations in the Z-disc components found in HCM and DCM may result in increased and decreased stiffness of sarcomere; that is, stiff sarcomere and loose sarcomere, respectively, and hence altered stretch response. More recently, mutations in the components of I region were found in hereditary Cardiomyopathy and the functional analyses of the mutations suggested that the altered stress response was associated with Cardiomyopathy, further complicating the etiology and pathogenesis. However, elucidation of genetic etiology and functional alterations caused by the mutations shed lights on the new therapeutic approaches to hereditary Cardiomyopathy, such that treatment of DCM with a Ca^2+ sensitizer prevented the disease in a mouse model.
