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Junichi Sadoshima - One of the best experts on this subject based on the ideXlab platform.
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mechanisms of physiological and pathological cardiac Hypertrophy
Nature Reviews Cardiology, 2018Co-Authors: Michinari Nakamura, Junichi SadoshimaAbstract:Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number, individual cardiomyocytes increase in size, and the heart develops Hypertrophy to reduce ventricular wall stress and maintain function and efficiency in response to an increased workload. There are two types of Hypertrophy: physiological and pathological. Hypertrophy initially develops as an adaptive response to physiological and pathological stimuli, but pathological Hypertrophy generally progresses to heart failure. Each form of Hypertrophy is regulated by distinct cellular signalling pathways. In the past decade, a growing number of studies have suggested that previously unrecognized mechanisms, including cellular metabolism, proliferation, non-coding RNAs, immune responses, translational regulation, and epigenetic modifications, positively or negatively regulate cardiac Hypertrophy. In this Review, we summarize the underlying molecular mechanisms of physiological and pathological Hypertrophy, with a particular emphasis on the role of metabolic remodelling in both forms of cardiac Hypertrophy, and we discuss how the current knowledge on cardiac Hypertrophy can be applied to develop novel therapeutic strategies to prevent or reverse pathological Hypertrophy.
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GDF15, a Cardioprotective TGF- Superfamily Protein
2016Co-Authors: Tetsuro Ago, Junichi SadoshimaAbstract:The transforming growth factor- (TGF-) superfamilyproteins, comprising more than 40 members (broadlydivided into the TGF-s/activins/nodal family and the bone morphogenetic proteins [BMPs]/Müllerrian inhibiting substance/growth and differentiation factors [GDFs] family), were originally identified as molecules important for regulat-ing development, differentiation, and tissue repair in various organs.1 TGF-1, a founding member of the TGF- super-family, plays a key role in mediating cardiac Hypertrophy2 and remodeling after myocardial infarction (MI) as an auto-crine/paracrine factor.3 Increased TGF-1 expression is con-sidered one of the few molecular markers that potentially discriminate between compensated and decompensated car-diac Hypertrophy.3 Although TGF-1 may function protec-tively after MI by promoting scar formation, inhibiting neutrophil infiltration, and facilitating cardiomyogenic differ-entiation of adult hematopoietic stem cells,4 such beneficia
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gdf15 a cardioprotective tgf β superfamily protein
Circulation Research, 2006Co-Authors: Tetsuro Ago, Junichi SadoshimaAbstract:See related articles, pages 342–350 and 351–360 The transforming growth factor-β (TGF-β) superfamily proteins, comprising more than 40 members (broadly divided into the TGF-βs/activins/nodal family and the bone morphogenetic proteins [BMPs]/Mullerrian inhibiting substance/growth and differentiation factors [GDFs] family), were originally identified as molecules important for regulating development, differentiation, and tissue repair in various organs.1 TGF-β1, a founding member of the TGF-β superfamily, plays a key role in mediating cardiac Hypertrophy2 and remodeling after myocardial infarction (MI) as an autocrine/paracrine factor.3 Increased TGF-β1 expression is considered one of the few molecular markers that potentially discriminate between compensated and decompensated cardiac Hypertrophy.3 Although TGF-β1 may function protectively after MI by promoting scar formation, inhibiting neutrophil infiltration, and facilitating cardiomyogenic differentiation of adult hematopoietic stem cells,4 such beneficial effects last only briefly and sustained activation of TGF-β1 causes structural remodeling, eventually leading to cardiac failure.5 Thus, TGF-β1 is generally regarded as detrimental, inducing cardiac Hypertrophy and failure in the adult heart. Compared with the wealth of knowledge regarding the effects of TGF-β1 on the heart, much less is known as to how other members of the TGF-β superfamily affect cardiac Hypertrophy and failure.6 In this issue of Circulation Research , two companion articles report the effect of growth and differentiation factor 15 (GDF15), a 12-kDa secreted protein (and a 25-kDa disulfide-linked dimer) belonging to the TGF-β superfamily, on cardiac Hypertrophy and apoptosis.7,8 GDF15 is highly expressed in the placenta and the prostate, but not normally in many other organs, including the heart.9,10 However, expression of GDF15 is induced rapidly by IL-1, TNFα, and TGF-β in macrophages, thereby limiting macrophage activation and inflammation (Figure …
Ganganath Rodrigo - One of the best experts on this subject based on the ideXlab platform.
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isolated unilateral temporalis muscle Hypertrophy in a child a case report with literature review
BMC Pediatrics, 2018Co-Authors: Jagath Ranasinghe, Chandani Wickramasinghe, Ganganath RodrigoAbstract:Temporalis muscle Hypertrophy is a rare entity of masticatory muscle Hypertrophy. All types of masticatory muscle hypertrophies have been documented of which temporalis muscle Hypertrophy is one. Temporalis muscle Hypertrophy is most commonly bilateral and usually associated with other types of masticatory muscles Hypertrophy such as masseter or pterygoid Hypertrophy. However, isolated unilateral temporalis muscle Hypertrophy is extremely rare and only 9 cases have been reported to date in English literature since 1990 with only two patients less than 18 years. There is no exact etiology identified and the diagnosis is made by muscle biopsy combined with imaging study to exclude other possibilities. Age at presentation is ranges from 15 to 65 years with involvement of both sexes. We report the youngest child who is a seven year old girl with right side isolated unilateral temporalis muscle Hypertrophy. In this patient, we discuss the youngest child with isolated unilateral temporalis muscle Hypertrophy and literature review to date. The patient is a seven year old female presenting with painless swelling of the right temporalis muscle. There had no features of inflammation, trauma, neoplasm or history of parafunctions such as bruxism. The child was not complaining significantly headache or visual disturbances as well. She had undergone radiological assessment with ultrasound scan and contrast MRI. The diagnosis was confirmed by muscle biopsy which shows normal muscle architecture. She was managed conservatively with regular follow up. Isolated unilateral temporalis muscle Hypertrophy is extremely rare in children. However this case raises the importance of considering alternative diagnoses despite the condition being rare in the pediatric population.
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Isolated unilateral temporalis muscle Hypertrophy in a child: a case report with literature review
'Springer Science and Business Media LLC', 2018Co-Authors: Jagath C. Ranasinghe, Chandani Wickramasinghe, Ganganath RodrigoAbstract:Abstract Background Temporalis muscle Hypertrophy is a rare entity of masticatory muscle Hypertrophy. All types of masticatory muscle hypertrophies have been documented of which temporalis muscle Hypertrophy is one. Temporalis muscle Hypertrophy is most commonly bilateral and usually associated with other types of masticatory muscles Hypertrophy such as masseter or pterygoid Hypertrophy. However, isolated unilateral temporalis muscle Hypertrophy is extremely rare and only 9 cases have been reported to date in English literature since 1990 with only two patients less than 18 years. There is no exact etiology identified and the diagnosis is made by muscle biopsy combined with imaging study to exclude other possibilities. Age at presentation is ranges from 15 to 65 years with involvement of both sexes. We report the youngest child who is a seven year old girl with right side isolated unilateral temporalis muscle Hypertrophy. Case presentation In this patient, we discuss the youngest child with isolated unilateral temporalis muscle Hypertrophy and literature review to date. The patient is a seven year old female presenting with painless swelling of the right temporalis muscle. There had no features of inflammation, trauma, neoplasm or history of parafunctions such as bruxism. The child was not complaining significantly headache or visual disturbances as well. She had undergone radiological assessment with ultrasound scan and contrast MRI. The diagnosis was confirmed by muscle biopsy which shows normal muscle architecture. She was managed conservatively with regular follow up. Conclusion Isolated unilateral temporalis muscle Hypertrophy is extremely rare in children. However this case raises the importance of considering alternative diagnoses despite the condition being rare in the pediatric population
Nipavan Chiamvimonvat - One of the best experts on this subject based on the ideXlab platform.
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soluble epoxide hydrolase plays an essential role in angiotensin ii induced cardiac Hypertrophy
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Wei Pang, Nipavan Chiamvimonvat, Paul D Jones, Jun Yang, Youyi Zhang, John Y J Shyy, Bruce D Hammock, Yi ZhuAbstract:Pathophysiological cardiac Hypertrophy is one of the most common causes of heart failure. Epoxyeicosatrienoic acids, hydrolyzed and degraded by soluble epoxide hydrolase (sEH), can function as endothelium-derived hyperpolarizing factors to induce dilation of coronary arteries and thus are cardioprotective. In this study, we investigated the role of sEH in two rodent models of angiotensin II (Ang II)-induced cardiac Hypertrophy. The protein level of sEH was elevated in the heart of both spontaneously hypertensive rats and Ang II-infused Wistar rats. Blocking the Ang II type 1 receptor with losartan could abolish this induction. Administration of a potent sEH inhibitor (sEHI) prevented the pathogenesis of the Ang II-induced Hypertrophy, as demonstrated by decreased left-ventricular Hypertrophy assessed by echocardiography, reduced cardiomyocyte size, and attenuated expression of Hypertrophy markers, including atrial natriuretic factor and β-myosin heavy chain. Because sEH elevation was not observed in exercise- or norepinephrine-induced Hypertrophy, the sEH induction was closely associated with Ang II-induced Hypertrophy. In vitro, Ang II upregulated sEH and Hypertrophy markers in neonatal cardiomyocytes isolated from rat and mouse. Expression of these marker genes was elevated with adenovirus-mediated sEH overexpression but decreased with sEHI treatment. These results were supported by studies in neonatal cardiomyocytes from sEH−/− mice. Our results suggest that sEH is specifically upregulated by Ang II, which directly mediates Ang II-induced cardiac Hypertrophy. Thus, pharmacological inhibition of sEH would be a useful approach to prevent and treat Ang II-induced cardiac Hypertrophy.
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prevention and reversal of cardiac Hypertrophy by soluble epoxide hydrolase inhibitors
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Valeriy Timofeyev, Hsing Ju Tsai, In Hae Kim, Benjamin B. Davis, Dipika Tuteja, Robertino Karlo P Mateo, Anil Singapuri, Reginald I Low, Nipavan ChiamvimonvatAbstract:Sustained cardiac Hypertrophy represents one of the most common causes leading to cardiac failure. There is emerging evidence to implicate the involvement of NF-κB in the development of cardiac Hypertrophy. However, several critical questions remain unanswered. We tested the use of soluble epoxide hydrolase (sEH) inhibitors as a means to enhance the biological activities of epoxyeicosatrienoic acids (EETs) to treat cardiac Hypertrophy. sEH catalyzes the conversion of EETs to form the corresponding dihydroxyeicosatrienoic acids. Previous data have suggested that EETs may inhibit the activation of NF-κB-mediated gene transcription. We directly demonstrate the beneficial effects of several potent sEH inhibitors (sEHIs) in cardiac Hypertrophy. Specifically, we show that sEHIs can prevent the development of cardiac Hypertrophy using a murine model of pressure-induced cardiac Hypertrophy. In addition, sEHIs reverse the preestablished cardiac Hypertrophy caused by chronic pressure overload. We further demonstrate that these compounds potently block the NF-κB activation in cardiac myocytes. Moreover, by using in vivo electrophysiologic recordings, our study shows a beneficial effect of the compounds in the prevention of cardiac arrhythmias that occur in association with cardiac Hypertrophy. We conclude that the use of sEHIs to increase the level of the endogenous lipid epoxides such as EETs may represent a viable and completely unexplored avenue to reduce cardiac Hypertrophy by blocking NF-κB activation.
Yi Zhu - One of the best experts on this subject based on the ideXlab platform.
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soluble epoxide hydrolase plays an essential role in angiotensin ii induced cardiac Hypertrophy
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Wei Pang, Nipavan Chiamvimonvat, Paul D Jones, Jun Yang, Youyi Zhang, John Y J Shyy, Bruce D Hammock, Yi ZhuAbstract:Pathophysiological cardiac Hypertrophy is one of the most common causes of heart failure. Epoxyeicosatrienoic acids, hydrolyzed and degraded by soluble epoxide hydrolase (sEH), can function as endothelium-derived hyperpolarizing factors to induce dilation of coronary arteries and thus are cardioprotective. In this study, we investigated the role of sEH in two rodent models of angiotensin II (Ang II)-induced cardiac Hypertrophy. The protein level of sEH was elevated in the heart of both spontaneously hypertensive rats and Ang II-infused Wistar rats. Blocking the Ang II type 1 receptor with losartan could abolish this induction. Administration of a potent sEH inhibitor (sEHI) prevented the pathogenesis of the Ang II-induced Hypertrophy, as demonstrated by decreased left-ventricular Hypertrophy assessed by echocardiography, reduced cardiomyocyte size, and attenuated expression of Hypertrophy markers, including atrial natriuretic factor and β-myosin heavy chain. Because sEH elevation was not observed in exercise- or norepinephrine-induced Hypertrophy, the sEH induction was closely associated with Ang II-induced Hypertrophy. In vitro, Ang II upregulated sEH and Hypertrophy markers in neonatal cardiomyocytes isolated from rat and mouse. Expression of these marker genes was elevated with adenovirus-mediated sEH overexpression but decreased with sEHI treatment. These results were supported by studies in neonatal cardiomyocytes from sEH−/− mice. Our results suggest that sEH is specifically upregulated by Ang II, which directly mediates Ang II-induced cardiac Hypertrophy. Thus, pharmacological inhibition of sEH would be a useful approach to prevent and treat Ang II-induced cardiac Hypertrophy.
Paul D Jones - One of the best experts on this subject based on the ideXlab platform.
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soluble epoxide hydrolase plays an essential role in angiotensin ii induced cardiac Hypertrophy
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Wei Pang, Nipavan Chiamvimonvat, Paul D Jones, Jun Yang, Youyi Zhang, John Y J Shyy, Bruce D Hammock, Yi ZhuAbstract:Pathophysiological cardiac Hypertrophy is one of the most common causes of heart failure. Epoxyeicosatrienoic acids, hydrolyzed and degraded by soluble epoxide hydrolase (sEH), can function as endothelium-derived hyperpolarizing factors to induce dilation of coronary arteries and thus are cardioprotective. In this study, we investigated the role of sEH in two rodent models of angiotensin II (Ang II)-induced cardiac Hypertrophy. The protein level of sEH was elevated in the heart of both spontaneously hypertensive rats and Ang II-infused Wistar rats. Blocking the Ang II type 1 receptor with losartan could abolish this induction. Administration of a potent sEH inhibitor (sEHI) prevented the pathogenesis of the Ang II-induced Hypertrophy, as demonstrated by decreased left-ventricular Hypertrophy assessed by echocardiography, reduced cardiomyocyte size, and attenuated expression of Hypertrophy markers, including atrial natriuretic factor and β-myosin heavy chain. Because sEH elevation was not observed in exercise- or norepinephrine-induced Hypertrophy, the sEH induction was closely associated with Ang II-induced Hypertrophy. In vitro, Ang II upregulated sEH and Hypertrophy markers in neonatal cardiomyocytes isolated from rat and mouse. Expression of these marker genes was elevated with adenovirus-mediated sEH overexpression but decreased with sEHI treatment. These results were supported by studies in neonatal cardiomyocytes from sEH−/− mice. Our results suggest that sEH is specifically upregulated by Ang II, which directly mediates Ang II-induced cardiac Hypertrophy. Thus, pharmacological inhibition of sEH would be a useful approach to prevent and treat Ang II-induced cardiac Hypertrophy.
