The Experts below are selected from a list of 30597 Experts worldwide ranked by ideXlab platform
Vihang A Narkar - One of the best experts on this subject based on the ideXlab platform.
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exercise and pgc 1α independent synchronization of type i muscle metabolism and vasculature by errγ
Cell Metabolism, 2011Co-Authors: Vihang A Narkar, Michael Downes, Ruth T Yu, Johan W Jonker, William A Alaynick, Ester Banayo, Malith S Karunasiri, Sabina Lorca, Ronald M EvansAbstract:Summary How type I skeletal muscle inherently maintains high oxidative and Vascular Capacity in the absence of exercise is unclear. We show that nuclear receptor ERRγ is highly expressed in type I muscle and, when transgenically expressed in anaerobic type II muscles (ERRGO mice), dually induces metabolic and Vascular transformation in the absence of exercise. ERRGO mice show increased expression of genes promoting fat metabolism, mitochondrial respiration, and type I fiber specification. Muscles in ERRGO mice also display an activated angiogenic program marked by myofibrillar induction and secretion of proangiogenic factors, neoVascularization, and a 100% increase in running endurance. Surprisingly, the induction of type I muscle properties by ERRγ does not involve PGC-1α. Instead, ERRγ genetically activates the energy sensor AMPK in mediating the metaboVascular changes in ERRGO mice. Therefore, ERRγ represents a previously unrecognized determinant that specifies intrinsic Vascular and oxidative metabolic features that distinguish type I from type II muscle.
N B Anthony - One of the best experts on this subject based on the ideXlab platform.
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pulmonary arterial hypertension ascites syndrome in broilers a review
Poultry Science, 2013Co-Authors: R F Wideman, G F Erf, Douglas D Rhoads, N B AnthonyAbstract:Pulmonary arterial hypertension (PAH) syndrome in broilers (also known as ascites syndrome and pulmonary hypertension syndrome) can be attributed to imbalances between cardiac output and the anatomical Capacity of the pulmonary vasculature to accommodate ever-increasing rates of blood flow, as well as to an inappropriately elevated tone (degree of constriction) maintained by the pulmonary arterioles. Comparisons of PAH-susceptible and PAH-resistant broilers do not consistently reveal differences in cardiac output, but PAH-susceptible broilers consistently have higher pulmonary arterial pressures and pulmonary Vascular resistances compared with PAH-resistant broilers. Efforts clarify the causes of excessive pulmonary Vascular resistance have focused on evaluating the roles of chemical mediators of vasoconstriction and vasodilation, as well as on pathological (structural) changes occurring within the pulmonary arterioles (e.g., Vascular remodeling and pathology) during the pathogenesis of PAH. The objectives of this review are to (1) summarize the pathophysiological progression initiated by the onset of pulmonary hypertension and culminating in terminal ascites; (2) review recent information regarding the factors contributing to excessively elevated resistance to blood flow through the lungs; (3) assess the role of the immune system during the pathogenesis of PAH; and (4) present new insights into the genetic basis of PAH. The cumulative evidence attributes the elevated pulmonary Vascular resistance in PAH-susceptible broilers to an anatomically inadequate pulmonary Vascular Capacity, to excessive Vascular tone reflecting the dominance of pulmonary vasoconstrictors over vasodilators, and to Vascular pathology elicited by excessive hemodynamic stress. Emerging evidence also demonstrates that the pathogenesis of PAH includes characteristics of an inflammatory/autoimmune disease involving multifactorial genetic, environmental, and immune system components. Pulmonary arterial hypertension susceptibility appears to be multigenic and may be manifested in aberrant stress sensitivity, function, and regulation of pulmonary Vascular tissue components, as well as aberrant activities of innate and adaptive immune system components. Major genetic influences and high heritabilities for PAH susceptibility have been demonstrated by numerous investigators. Selection pressures rigorously focused to challenge the pulmonary Vascular Capacity readily expose the genetic basis for spontaneous PAH in broilers. Chromosomal mapping continues to identify regions associated with ascites susceptibility, and candidate genes have been identified. Ongoing immunological and genomic investigations are likely to continue generating important new knowledge regarding the fundamental biological bases for the PAH/ascites syndrome.
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an inadequate pulmonary Vascular Capacity and susceptibility to pulmonary arterial hypertension in broilers
Poultry Science, 2007Co-Authors: R F Wideman, M E Chapman, Krishna R Hamal, O T Bowen, A G Lorenzoni, G F Erf, N B AnthonyAbstract:Broilers are susceptible to pulmonary hypertension syndrome (PHS; ascites syndrome) when their pulmonary Vascular Capacity is anatomically or functionally inadequate to accommodate the requisite cardiac output without an excessive elevation in pulmonary arterial pressure. The consequences of an inadequate pulmonary Vascular Capacity have been demonstrated experimentally and include elevated pulmonary Vascular resistance (PVR) attributable to noncompliant, fully engorged Vascular channels; sustained pulmonary arterial hypertension (PAH); systemic hypoxemia and hypercapnia; specific right ventricular hypertrophy, and right atrioventricular valve failure (regurgitation), leading to central venous hypertension and hepatic cirrhosis. Pulmonary Vascular Capacity is broadly defined to encompass anatomical constraints related to the compliance and effective volume of blood vessels, as well as functional limitations related to the tone (degree of constriction) maintained by the primary resistance vessels (arterioles) within the lungs. Surgical occlusion of 1 pulmonary artery halves the anatomical pulmonary Vascular Capacity, doubles the PVR, triggers PAH, eliminates PHS-susceptible broilers, and reveals PHS-resistant survivors whose lungs are innately capable of handling sustained increases in pulmonary arterial pressure and cardiac output. We currently are using i.v. microparticle injections to increase the PVR and trigger PAH sufficient in magnitude to eliminate PHS-susceptible individuals while allowing PHS-resistant individuals to survive as progenitors of robust broiler lines. The microparticles obstruct pulmonary arterioles and cause local tissues and responding leukocytes to release vasoactive substances, including the vasodilator NO and the highly effective vasoconstrictors thromboxane A(2) and serotonin [5-hydroxytryptamine (5-HT)]. Nitric oxide is the principal vasodilator responsible for modulating (attenuating) the PAH response and ensuing mortality triggered by i.v. microparticle injections, whereas microparticle-induced increases in PVR can be attributed principally to 5-HT. Our observations support the hypothesis that susceptibility to PHS is a consequence of anatomically inadequate pulmonary Vascular Capacity combined with the functional predominance of the vasoconstrictor 5-HT over the vasodilator NO. The contribution of TxA(2) remains to be determined. Selecting broiler lines for resistance to PHS depends upon improving both anatomical and functional components of pulmonary Vascular Capacity.
Sookyoung Choi - One of the best experts on this subject based on the ideXlab platform.
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adiporon adiponectin receptor agonist improves Vascular function in the mesenteric arteries of type 2 diabetic mice
Journal of Infectious Diseases and Therapy, 2019Co-Authors: Sookyoung ChoiAbstract:Adiponectin is one of the most abundant adipokines secreted from adipose tissue. An orally active synthetic adiponectin receptor agonist, adipoRon has been suggested to ameliorate insulin resistance, myocardial apoptosis, and pancreatic tumor. It has been reported that adiponectin directly induces Vascular relaxation however; the chronic effect of adipoRon in the Vascular dysfunction in type 2 diabetes has not been studied yet. Thus, in this study, we examined whether adipoRon improves Vascular function in type 2 diabetes and what mechanism is involved. Ten to 12-week old male type 2 diabetic (db-/ db-) mice were treated with adiponectin receptor agonist (adipoRon, 10 mg/kg/everyday by oral gavage) for 2 weeks. Isolated mesenteric arteries were mounted in the arteriography and arterial diameter was measured. And western blot analysis was assessed. Pressure-induced myogenic response was significantly increased, whereas endothelium-dependent relaxation was significantly reduced in the mesenteric arteries from type 2 diabetic mice. Interestingly, treatment of adipoRon normalized potentiated myogenic response. However, endothelium-dependent relaxation was not affected by treatment of adipoRon. The expression levels of adiponectin receptor 1, 2 and APPL 1, 2 were increased in the mesenteric arteries from Type 2 diabetic mice and treatment of adipoRon did not affect them. Interestingly, adipoRon treatment increased the phosphorylation level of AMPK and decreased phosphorylation of MYPT1 in the type 2 diabetic mice while there was no change in the level of eNOS phosphorylation. The treatment of adipoRon improves Vascular function in the mesenteric arteries from type 2 diabetic mice through endothelium-independent mechanism. It is suggested that MLCP activation through reduced phosphorylation of MYPT1 might be the dominant mechanism in the adipoRon-induced Vascular effect. Stoutness is characterized as an extreme and irregular fat collection to apply wellbeing concerns. Heftiness is viewed as the main consideration in the advancement of different malady, for example, type 2 diabetes, hypertension, cardioVascular ailment, respiratory illness, and osteo-joint inflammation . Collecting proof shows that heftiness every now and again happens with type 2 diabetes and is viewed as a solid hazard factor for the advancement of type 2 diabetes . Heftiness and type 2 diabetes effectsly affect Vascular Capacity and make conditions that favor cardioVascular illness .Adiponectin is a significant and copious adipokine emitted from adipocyte and directs insulin affectability and vitality homeostasis. The low centralization of adiponectin is related with different infection, for example, weight, diabetes, cardioVascular sicknesses. Late examinations revealed plasma adiponectin level was diminished in the patients with type 2 diabetes, and thiazolidinedione (TZD) organization expanded the adiponectinlevel . A trial study indicated that insulin opposition was enhanced by the renewal of adiponectin in mice . In this way adiponectin has been engaged as likely restorative objective for the treatment of type 2 diabetes .Adiponectin directs cell work by means of two explicit receptors, adiponectin receptor 1 (AdiR1) and adiponectin receptor 2 (AdiR2) . Connector protein containing a pleckstrin homology (PH) space, phosphotyrosine-official (PTB) area, and leucine zipper theme 1 (APPL1) is the primary recognized connector protein to emphatically intervene intracellular adiponectin flagging. APPL1 straightforwardly ties to the intracellular area of adiponectin receptor and decidedly intervenes the motioning to the AMP-initiated protein kinase (AMPK), p38 mitogen enacted protein kinase (MAPK), and peroxisome proliferator-actuated receptor α (PPARα) . Then again APPL2, an isoform of APPL1, squares APPL1-intervened insulin-sharpening impact of adiponectin and in this way adversely directs adiponectinflagging . As of late, an orally dynamic adiponectin receptor agonist, AdipoRon, has been created and demonstrated comparative impacts to adiponectin. Like adiponectin, AdipoRon ties to both AdiR1 and AdiR2 at a low atomic focus and enacts AMPK, PPAR, and peroxisome proliferator–initiated receptor gamma coactivator 1–alpha (PGC1α). AdipoRon improved insulin affectability and glucose resilience and lipid digestion in refined cells and mice. Moreover, treatment of AdipoRon improved metabolic Capacity and broadened life range in type 2 diabetic mice. Ten-to 12-week-old male sort 2 diabetic mice (db−/db−) and age-coordinated heterozygote control mice (db−/db+) were acquired from Jackson Laboratories. Mice were housed in an AAALAC endorsed creature office at Yonsei University. Quickly, mice were housed in plastic enclosures with hardened steel framework tops at 23~24°C with a 12-hour light/dim cycle and permitted access to business rat chow and water not indispensable. Absolute 30 diabetic mice and 20 control mice were utilized in this examination. Mice were separated into 4 gatherings: (1) control mice rewarded with vehicle for about fourteen days (control mice); (2) control mice rewarded with AdipoRon (10 mg/kg/ordinarily, by oral gavage) for about fourteen days; (3) diabetic mice rewarded with vehicle for about fourteen days (diabetic mice); (4) diabetic mice rewarded with AdipoRon (10 mg/kg/regularly, by oral gavage) for about fourteen days. Body weight and blood glucose levels were recorded each other day during the trial time frame. Toward the finish of the treatment time frame, mice were euthanized with isoflurane (5%) trailed by the CO2 inward breath. To affirm demise, we checked mice for the few signs, for example, no rising and falling of chest, no reaction to toe squeeze, no substantial heartbeat, shading change obscurity in eyes. After we affirm the passing, the heart was expelled quickly and tissue tests were gotten. To confine mesenteric supply route, the mesenteric little vein beds were expelled and set in super cold Krebs-Henseleit (K-H) arrangement (creation in mmol/L: NaCl, 119; CaCl2, 2.5; NaHCO3, 25; MgSO4, 1.2; KH2PO4, 1.2; KCl, 4.6; and glucose, 11.1). The third part of mesenteric veins (120–150 μm, inward distance across at 40 mmHg) were confined and sliced into 2-to 3-mm sections for ensuing examination. As of late, an orally dynamic adiponectin receptor agonist, AdipoRon, has been created and demonstrated comparable impacts to adiponectin. Like adiponectin, AdipoRon ties to both AdiR1 and AdiR2 at a low atomic fixation and enacts AMPK, PPAR, and peroxisome proliferator–actuated receptor gamma coactivator 1–alpha (PGC1α). AdipoRon improved insulin affectability and glucose resistance and lipid digestion in refined cells and mice . Moreover, treatment of AdipoRon improved metabolic Capacity and expanded life expectancy in type 2 diabetic mice. In spite of the fact that impacts of AdipoRon have been researched in different pathophysiological states, the impacts of AdipoRon on Vascular Capacity, explicitly in type 2 diabetes have not yet been contemplated. Along these lines, the targets of the current investigation were to explain whether adiponectin receptor agonist, AdipoRon, improves Vascular Capacity in the mesenteric supply routes of type 2 diabetic mice and, provided that this is true, to decide the systems in question.
Ronald M Evans - One of the best experts on this subject based on the ideXlab platform.
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exercise and pgc 1α independent synchronization of type i muscle metabolism and vasculature by errγ
Cell Metabolism, 2011Co-Authors: Vihang A Narkar, Michael Downes, Ruth T Yu, Johan W Jonker, William A Alaynick, Ester Banayo, Malith S Karunasiri, Sabina Lorca, Ronald M EvansAbstract:Summary How type I skeletal muscle inherently maintains high oxidative and Vascular Capacity in the absence of exercise is unclear. We show that nuclear receptor ERRγ is highly expressed in type I muscle and, when transgenically expressed in anaerobic type II muscles (ERRGO mice), dually induces metabolic and Vascular transformation in the absence of exercise. ERRGO mice show increased expression of genes promoting fat metabolism, mitochondrial respiration, and type I fiber specification. Muscles in ERRGO mice also display an activated angiogenic program marked by myofibrillar induction and secretion of proangiogenic factors, neoVascularization, and a 100% increase in running endurance. Surprisingly, the induction of type I muscle properties by ERRγ does not involve PGC-1α. Instead, ERRγ genetically activates the energy sensor AMPK in mediating the metaboVascular changes in ERRGO mice. Therefore, ERRγ represents a previously unrecognized determinant that specifies intrinsic Vascular and oxidative metabolic features that distinguish type I from type II muscle.
R F Wideman - One of the best experts on this subject based on the ideXlab platform.
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pulmonary arterial hypertension ascites syndrome in broilers a review
Poultry Science, 2013Co-Authors: R F Wideman, G F Erf, Douglas D Rhoads, N B AnthonyAbstract:Pulmonary arterial hypertension (PAH) syndrome in broilers (also known as ascites syndrome and pulmonary hypertension syndrome) can be attributed to imbalances between cardiac output and the anatomical Capacity of the pulmonary vasculature to accommodate ever-increasing rates of blood flow, as well as to an inappropriately elevated tone (degree of constriction) maintained by the pulmonary arterioles. Comparisons of PAH-susceptible and PAH-resistant broilers do not consistently reveal differences in cardiac output, but PAH-susceptible broilers consistently have higher pulmonary arterial pressures and pulmonary Vascular resistances compared with PAH-resistant broilers. Efforts clarify the causes of excessive pulmonary Vascular resistance have focused on evaluating the roles of chemical mediators of vasoconstriction and vasodilation, as well as on pathological (structural) changes occurring within the pulmonary arterioles (e.g., Vascular remodeling and pathology) during the pathogenesis of PAH. The objectives of this review are to (1) summarize the pathophysiological progression initiated by the onset of pulmonary hypertension and culminating in terminal ascites; (2) review recent information regarding the factors contributing to excessively elevated resistance to blood flow through the lungs; (3) assess the role of the immune system during the pathogenesis of PAH; and (4) present new insights into the genetic basis of PAH. The cumulative evidence attributes the elevated pulmonary Vascular resistance in PAH-susceptible broilers to an anatomically inadequate pulmonary Vascular Capacity, to excessive Vascular tone reflecting the dominance of pulmonary vasoconstrictors over vasodilators, and to Vascular pathology elicited by excessive hemodynamic stress. Emerging evidence also demonstrates that the pathogenesis of PAH includes characteristics of an inflammatory/autoimmune disease involving multifactorial genetic, environmental, and immune system components. Pulmonary arterial hypertension susceptibility appears to be multigenic and may be manifested in aberrant stress sensitivity, function, and regulation of pulmonary Vascular tissue components, as well as aberrant activities of innate and adaptive immune system components. Major genetic influences and high heritabilities for PAH susceptibility have been demonstrated by numerous investigators. Selection pressures rigorously focused to challenge the pulmonary Vascular Capacity readily expose the genetic basis for spontaneous PAH in broilers. Chromosomal mapping continues to identify regions associated with ascites susceptibility, and candidate genes have been identified. Ongoing immunological and genomic investigations are likely to continue generating important new knowledge regarding the fundamental biological bases for the PAH/ascites syndrome.
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an inadequate pulmonary Vascular Capacity and susceptibility to pulmonary arterial hypertension in broilers
Poultry Science, 2007Co-Authors: R F Wideman, M E Chapman, Krishna R Hamal, O T Bowen, A G Lorenzoni, G F Erf, N B AnthonyAbstract:Broilers are susceptible to pulmonary hypertension syndrome (PHS; ascites syndrome) when their pulmonary Vascular Capacity is anatomically or functionally inadequate to accommodate the requisite cardiac output without an excessive elevation in pulmonary arterial pressure. The consequences of an inadequate pulmonary Vascular Capacity have been demonstrated experimentally and include elevated pulmonary Vascular resistance (PVR) attributable to noncompliant, fully engorged Vascular channels; sustained pulmonary arterial hypertension (PAH); systemic hypoxemia and hypercapnia; specific right ventricular hypertrophy, and right atrioventricular valve failure (regurgitation), leading to central venous hypertension and hepatic cirrhosis. Pulmonary Vascular Capacity is broadly defined to encompass anatomical constraints related to the compliance and effective volume of blood vessels, as well as functional limitations related to the tone (degree of constriction) maintained by the primary resistance vessels (arterioles) within the lungs. Surgical occlusion of 1 pulmonary artery halves the anatomical pulmonary Vascular Capacity, doubles the PVR, triggers PAH, eliminates PHS-susceptible broilers, and reveals PHS-resistant survivors whose lungs are innately capable of handling sustained increases in pulmonary arterial pressure and cardiac output. We currently are using i.v. microparticle injections to increase the PVR and trigger PAH sufficient in magnitude to eliminate PHS-susceptible individuals while allowing PHS-resistant individuals to survive as progenitors of robust broiler lines. The microparticles obstruct pulmonary arterioles and cause local tissues and responding leukocytes to release vasoactive substances, including the vasodilator NO and the highly effective vasoconstrictors thromboxane A(2) and serotonin [5-hydroxytryptamine (5-HT)]. Nitric oxide is the principal vasodilator responsible for modulating (attenuating) the PAH response and ensuing mortality triggered by i.v. microparticle injections, whereas microparticle-induced increases in PVR can be attributed principally to 5-HT. Our observations support the hypothesis that susceptibility to PHS is a consequence of anatomically inadequate pulmonary Vascular Capacity combined with the functional predominance of the vasoconstrictor 5-HT over the vasodilator NO. The contribution of TxA(2) remains to be determined. Selecting broiler lines for resistance to PHS depends upon improving both anatomical and functional components of pulmonary Vascular Capacity.
