The Experts below are selected from a list of 30786 Experts worldwide ranked by ideXlab platform
Julia Buján - One of the best experts on this subject based on the ideXlab platform.
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Potassium Channel Openers Increase Aortic Elastic Fiber Formation and Reverse the Genetically Determined Elastin Deficit in the BN Rat
Hypertension, 2013Co-Authors: Séverin Slove, Morgane Lannoy, Jacques Behmoaras, Mylène Pezet, Natacha Sloboda, Patrick Lacolley, Brigitte Escoubet, Julia Buján, Marie-paule JacobAbstract:Hypertension is a Cardiovascular Disorder that appears in more than half of the patients with Williams-Beuren syndrome, hemizygous for the elastin gene among 26 to 28 other genes. It was shown that the antihypertensive drug minoxidil, an ATP-dependent potassium channel opener, enhances elastic fiber formation; however, no wide clinical application was developed because of its adverse side effects. The Brown Norway rat was used here as an arterial elastin-deficient model. We tested 3 different potassium channel openers, minoxidil, diazoxide, and pinacidil, and 1 potassium channel blocker, glibenclamide, on cultured smooth muscle cells from Brown Norway rat aorta. All tested potassium channel openers increased mRNAs encoding proteins and enzymes involved in elastic fiber formation, whereas glibenclamide had the opposite effect. The higher steady-state level of tropoelastin mRNA in minoxidil-treated cells was attributable to an increase in both transcription and mRNA stability. Treatment of Brown Norway rats for 10 weeks with minoxidil or diazoxide increased elastic fiber content and decreased cell number in the aortic media, without changing collagen content. The minoxidil-induced cardiac hypertrophy was reduced when animals simultaneously received irbesartan, an angiotensin II-receptor antagonist. This side effect of minoxidil was not observed in diazoxide-treated animals. In conclusion, diazoxide, causing less undesirable side effects than minoxidil, or coadministration of minoxidil and irbesartan, increases elastic fiber content, decreases cell number in the aorta and, thus, could be suitable for treating vascular pathologies characterized by diminished arterial elastin content and simultaneous hypertension.
Hitoshi Suzuki - One of the best experts on this subject based on the ideXlab platform.
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acute heart failure volume control multicenter randomized avcma trial comparison of tolvaptan and carperitide
The Journal of Clinical Pharmacology, 2013Co-Authors: Satoshi Suzuki, Akiomi Yoshihisa, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Yukihiko Abe, Tomiyoshi Saito, Takayuki Ohwada, Hitoshi SuzukiAbstract:Backgroud Acute decompensated heart failure (ADHF) is a common and highly morbid Cardiovascular Disorder. Diuresis is a major therapy for the reduction of congestive symptoms. However, most diuretics cause hyponatremia, which is a worsening factor of ADHF patients prognosis. The purpose of this study was to examine the efficacy and safety of tolvaptan, which is a selective vasopressin V2 receptor antagonist and produces water excretion without changes in sodium excretion, compared with carperitide.
Satoshi Suzuki - One of the best experts on this subject based on the ideXlab platform.
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Acute Heart Failure Volume Control Multicenter Randomized (AVCMA) Trial: Comparison of Tolvaptan and Carperitide
2016Co-Authors: Satoshi Suzuki, Akiomi Yoshihisa, Takayoshi YamakiAbstract:Yasuchika Takeishi, MD1, and on behalf of the AVCMA investigators† Backgroud: Acute decompensated heart failure (ADHF) is a common and highly morbid Cardiovascular Disorder. Diuresis is a major therapy for the reduction of congestive symptoms. However, most diuretics cause hyponatremia, which is a worsening factor of ADHF patients prognosis. The purpose of this study was to examine the efficacy and safety of tolvaptan, which is a selective vasopressin V2 receptor antagonist and produces water excretion without changes in sodium excretion, compared with carperitide. Methods and Results:One hundred and nine hospitalized ADHF patients were enrolled and randomly assigned to tolvaptan or carperitide treatment groups. Subjective symptoms and plasma BNP level were similarly improved by treatment in both groups. Urine volume was significantly higher in the tolvaptan group (P<.05), but volume of water intake was also higher in the tolvaptan group (P<.05). Blood pressure was significantly lower in the carperitide group than in the tolvaptan group after treatment (P<.05). Less adverse events such as worsening heart failure and hypotension requiring drug discontinuation were observed in the tolvaptan group (P .027). The average drug cost of tolvaptan was lower than that of carperitide (P<.001). Conclusions: Tolvaptan might be a novel promising agent for ADHF in terms of efficacy and safety compared to carperitide. Keywords acute decompensated heart failure, volume control, tolvaptan, carperitide Acute decompensated heart failure (ADHF) has emerge
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acute heart failure volume control multicenter randomized avcma trial comparison of tolvaptan and carperitide
The Journal of Clinical Pharmacology, 2013Co-Authors: Satoshi Suzuki, Akiomi Yoshihisa, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Yukihiko Abe, Tomiyoshi Saito, Takayuki Ohwada, Hitoshi SuzukiAbstract:Backgroud Acute decompensated heart failure (ADHF) is a common and highly morbid Cardiovascular Disorder. Diuresis is a major therapy for the reduction of congestive symptoms. However, most diuretics cause hyponatremia, which is a worsening factor of ADHF patients prognosis. The purpose of this study was to examine the efficacy and safety of tolvaptan, which is a selective vasopressin V2 receptor antagonist and produces water excretion without changes in sodium excretion, compared with carperitide.
Takayoshi Yamaki - One of the best experts on this subject based on the ideXlab platform.
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Acute Heart Failure Volume Control Multicenter Randomized (AVCMA) Trial: Comparison of Tolvaptan and Carperitide
2016Co-Authors: Satoshi Suzuki, Akiomi Yoshihisa, Takayoshi YamakiAbstract:Yasuchika Takeishi, MD1, and on behalf of the AVCMA investigators† Backgroud: Acute decompensated heart failure (ADHF) is a common and highly morbid Cardiovascular Disorder. Diuresis is a major therapy for the reduction of congestive symptoms. However, most diuretics cause hyponatremia, which is a worsening factor of ADHF patients prognosis. The purpose of this study was to examine the efficacy and safety of tolvaptan, which is a selective vasopressin V2 receptor antagonist and produces water excretion without changes in sodium excretion, compared with carperitide. Methods and Results:One hundred and nine hospitalized ADHF patients were enrolled and randomly assigned to tolvaptan or carperitide treatment groups. Subjective symptoms and plasma BNP level were similarly improved by treatment in both groups. Urine volume was significantly higher in the tolvaptan group (P<.05), but volume of water intake was also higher in the tolvaptan group (P<.05). Blood pressure was significantly lower in the carperitide group than in the tolvaptan group after treatment (P<.05). Less adverse events such as worsening heart failure and hypotension requiring drug discontinuation were observed in the tolvaptan group (P .027). The average drug cost of tolvaptan was lower than that of carperitide (P<.001). Conclusions: Tolvaptan might be a novel promising agent for ADHF in terms of efficacy and safety compared to carperitide. Keywords acute decompensated heart failure, volume control, tolvaptan, carperitide Acute decompensated heart failure (ADHF) has emerge
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acute heart failure volume control multicenter randomized avcma trial comparison of tolvaptan and carperitide
The Journal of Clinical Pharmacology, 2013Co-Authors: Satoshi Suzuki, Akiomi Yoshihisa, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Yukihiko Abe, Tomiyoshi Saito, Takayuki Ohwada, Hitoshi SuzukiAbstract:Backgroud Acute decompensated heart failure (ADHF) is a common and highly morbid Cardiovascular Disorder. Diuresis is a major therapy for the reduction of congestive symptoms. However, most diuretics cause hyponatremia, which is a worsening factor of ADHF patients prognosis. The purpose of this study was to examine the efficacy and safety of tolvaptan, which is a selective vasopressin V2 receptor antagonist and produces water excretion without changes in sodium excretion, compared with carperitide.
Kathleen M Ruppel - One of the best experts on this subject based on the ideXlab platform.
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early onset hypertrophic cardiomyopathy mutations significantly increase the velocity force and actin activated atpase activity of human β cardiac myosin
Cell Reports, 2016Co-Authors: Arjun S Adhikari, James A Spudich, Saswata S Sarkar, Chao Liu, Kristina B Kooiker, Daniel Bernstein, Kathleen M RuppelAbstract:Summary Hypertrophic cardiomyopathy (HCM) is a heritable Cardiovascular Disorder that affects 1 in 500 people. A significant percentage of HCM is attributed to mutations in β-cardiac myosin, the motor protein that powers ventricular contraction. This study reports how two early-onset HCM mutations, D239N and H251N, affect the molecular biomechanics of human β-cardiac myosin. We observed significant increases (20%–90%) in actin gliding velocity, intrinsic force, and ATPase activity in comparison to wild-type myosin. Moreover, for H251N, we found significantly lower binding affinity between the S1 and S2 domains of myosin, suggesting that this mutation may further increase hyper-contractility by releasing active motors. Unlike previous HCM mutations studied at the molecular level using human β-cardiac myosin, early-onset HCM mutations lead to significantly larger changes in the fundamental biomechanical parameters and show clear hyper-contractility.
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mutations in the catalytic domain of human β cardiac myosin that cause early onset hypertrophic cardiomyopathy significantly increase the fundamental parameters that determine ensemble force and velocity
bioRxiv, 2016Co-Authors: Arjun S Adhikari, James A Spudich, Saswata S Sarkar, Chao Liu, Kristina B Kooiker, Daniel Bernstein, Kathleen M RuppelAbstract:Hypertrophic cardiomyopathy (HCM) is a heritable Cardiovascular Disorder that affects 1 in 500 people. In infants it can be particularly severe and it is the leading cause of sudden cardiac death in pediatric populations. A high percentage of HCM is attributed to mutations in β-cardiac myosin, the motor protein that powers ventricular contraction. This study reports how two mutations that cause early-onset HCM, D239N and H251N, affect the mechanical output of human β-cardiac myosin at the molecular level. We observe extremely large increases (25% - 95%) in the actin gliding velocity, single molecule intrinsic force, and ATPase activity of the two mutant myosin motors compared to wild type myosin. In contrast to previous studies of HCM-causing mutations in human β-cardiac myosin, these mutations were striking in that they caused changes in biomechanical parameters that were both greater in magnitude and more uniformly consistent with a hyper-contractile phenotype. In addition, S1-S2 binding studies revealed a significant decrease in affinity of the H251N motor for S2, suggesting that this mutation may further increase hyper-contractility by releasing active motors from a sequestered state. This report shows, for the first time, a clear and significant gain in function for all tested molecular biomechanical parameters due to HCM mutations in human β-cardiac myosin.
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improved loaded in vitro motility assay and actin filament tracking software delineates the effect of hypertrophic and dilated cardiomyopathy mutations on the power output of cardiac myosin
Biophysical Journal, 2014Co-Authors: Tural Aksel, Masataka Kawana, Shirley Sutton, Kathleen M Ruppel, Arjun S Adhikari, James A SpudichAbstract:Hypertrophic (HCM) and dilated (DCM) cardiomyopathies are important causes of heart failure, arrhythmia, and sudden cardiac death. HCM is the most common heritable Cardiovascular Disorder, affecting 1 in 500 individuals, and is caused primarily by mutations that alter proteins of the cardiac sarcomere. Sarcomeric protein mutations are an increasingly recognized cause of familial DCM as well. HCM is associated with severe thickening of the left ventricular wall, preserved/increased systolic (contractile) and impaired diastolic (relaxation) function of the heart. DCM hearts have dilated left ventricular chambers and suffer from inadequate systolic activity. More than 300 point mutations in beta-cardiac myosin are associated with HCM or DCM. It is believed that HCM and DCM mutations increase and decrease respectively the power output of cardiac myosin which leads to a cascade of downstream signaling that gradually leads to the disease phenotype. To test this hypothesis it is essential to measure the power output of all HCM/DCM mutants in a high throughput manner. To quantitatively measure the load dependent myosin power output, we first improved the loaded in vitro motility assay (LIMA) by replacing load generating molecule alpha-actinin with alpha-catenin, which was generously provided by James Nelson at Stanford University. For accurate-and-fast data analysis, we developed a software called FAST that runs over parallel CPUs. Our initial results indicate that two HCM mutants (R719W, R403Q) have higher power output than the wildtype cardiac myosin. FAST-LIMA will be an essential tool for screening drugs that revert the effects of HCM/DCM mutations on the power output of beta-cardiac myosin.