scholarly journals ANOREXIGENIC AND CATABOLIC EFFECTS OF ANGIOTENSIN II ARE REDOX DEPENDENT: POTENTIAL MECHANISM OF CONGESTIVE HEART FAILURE-ASSOCIATED SKELETAL MUSCLE WASTING

2011 ◽  
Vol 57 (14) ◽  
pp. E366
Author(s):  
Sergiy Sukhanov ◽  
Laura Semrpun-Prieto ◽  
Tadashi Yoshida ◽  
Bashir Atteia ◽  
Romer Gonzalez-Villalobos ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Congestive Heart Failure ◽  
Angiotensin Ii ◽  
Muscle Wasting ◽  
Potential Mechanism ◽  
Skeletal Muscle Wasting ◽  
Dependent Potential

scholarly journals HDAC6 contributes to pathological responses of heart and skeletal muscle to chronic angiotensin-II signaling

2014 ◽  
Vol 307 (2) ◽  
pp. H252-H258 ◽  
Author(s):  
Kimberly M. Demos-Davies ◽  
Bradley S. Ferguson ◽  
Maria A. Cavasin ◽  
Jennifer H. Mahaffey ◽  
Sarah M. Williams ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Angiotensin Ii ◽  
Muscle Wasting ◽  
Striated Muscle ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Ang Ii ◽  
Skeletal Muscle Wasting

Little is known about the function of the cytoplasmic histone deacetylase HDAC6 in striated muscle. Here, we addressed the role of HDAC6 in cardiac and skeletal muscle remodeling induced by the peptide hormone angiotensin II (ANG II), which plays a central role in blood pressure control, heart failure, and associated skeletal muscle wasting. Comparable with wild-type (WT) mice, HDAC6 null mice developed cardiac hypertrophy and fibrosis in response to ANG II. However, whereas WT mice developed systolic dysfunction upon treatment with ANG II, cardiac function was maintained in HDAC6 null mice treated with ANG II for up to 8 wk. The cardioprotective effect of HDAC6 deletion was mimicked in WT mice treated with the small molecule HDAC6 inhibitor tubastatin A. HDAC6 null mice also exhibited improved left ventricular function in the setting of pressure overload mediated by transverse aortic constriction. HDAC6 inhibition appeared to preserve systolic function, in part, by enhancing cooperativity of myofibrillar force generation. Finally, we show that HDAC6 null mice are resistant to skeletal muscle wasting mediated by chronic ANG-II signaling. These findings define novel roles for HDAC6 in striated muscle and suggest potential for HDAC6-selective inhibitors for the treatment of cardiac dysfunction and muscle wasting in patients with heart failure.

scholarly journals A New Transgenic Mouse Model of Heart Failure and Cardiac Cachexia Raised by Sustained Activation of Met Tyrosine Kinase in the Heart

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Valentina Sala ◽  
Stefano Gatti ◽  
Simona Gallo ◽  
Enzo Medico ◽  
Daniela Cantarella ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Congestive Heart Failure ◽  
Body Weight ◽  
Transgenic Mouse ◽  
Muscle Wasting ◽  
Met Receptor ◽  
Cardiac Cachexia ◽  
New Model ◽  
Skeletal Muscle Wasting

Among other diseases characterized by the onset of cachexia, congestive heart failure takes a place of relevance, considering the high prevalence of this pathology in most European countries and in the United States, and is undergoing a rapid increase in developing countries. Actually, only few models of cardiac cachexia exist. Difficulties in the recruitment and follow-up of clinical trials implicate that new reproducible and well-characterized animal models are pivotal in developing therapeutic strategies for cachexia. We generated a new model of cardiac cachexia: a transgenic mouse expressing Tpr-Met receptor, the activated form of c-Met receptor of hepatocyte growth factor, specifically in the heart. We showed that the cardiac-specific induction of Tpr-Met raises a cardiac hypertrophic remodelling, which progresses into concentric hypertrophy with concomitant increase in Gdf15 mRNA levels. Hypertrophy progresses to congestive heart failure with preserved ejection fraction, characterized by reduced body weight gain and food intake and skeletal muscle wasting. Prevention trial by suppressing Tpr-Met showed that loss of body weight could be prevented. Skeletal muscle wasting was also associated with altered gene expression profiling. We propose transgenic Tpr-Met mice as a new model of cardiac cachexia, which will constitute a powerful tool to understand such complex pathology and test new drugs/approaches at the preclinical level.

scholarly journals Loop diuretic use is associated with skeletal muscle wasting in patients with heart failure

2020 ◽  
Vol 76 (1) ◽  
pp. 109-114
Author(s):  
Ippei Nakano ◽  
Masaya Tsuda ◽  
Shintaro Kinugawa ◽  
Arata Fukushima ◽  
Naoya Kakutani ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Loop Diuretic ◽  
Skeletal Muscle Wasting ◽  
Patients With Heart Failure

Abstract 13433: Angiotensin II Type 2 Receptor Regulates Skeletal Myoblast Differentiation: Implications for treatment of Cachexia and Skeletal Muscle Wasting

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tadashi Yoshida ◽  
Patrice Delafontaine
Keyword(s):  
Skeletal Muscle ◽  
Angiotensin Ii ◽  
Muscle Regeneration ◽  
Muscle Wasting ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Muscle Physiology ◽  
Ang Ii ◽  
Skeletal Muscle Wasting

Patients with advanced congestive heart failure (CHF) or chronic kidney disease (CKD) often have increased angiotensin II (Ang II) levels and cachexia. We previously demonstrated that Ang II infusion in rodents causes skeletal muscle wasting and decreases muscle regenerative potential via Ang II type 1 receptor (AT1R) signaling, likely contributing to cachexia in CHF and CKD. However, the potential role of Ang II type 2 receptor (AT2R) signaling in skeletal muscle physiology remains unknown. We found that AT2R expression was robustly increased in mouse skeletal myoblasts during differentiation, suggesting that the AT2R plays an important role in skeletal muscle regeneration. To test this hypothesis, we infused mice with AT2R antagonist PD123319 (PD, 30 mg/kg/d) or agonist CGP123319 (CGP, 1 μg/kg/min) during cardiotoxin (CTX)-induced muscle injury and regeneration. PD reduced the size of regenerating myofibers (727.5±54.6 and 516.0±37.0 μm2 in sham and PD, respectively, p<0.05) and expression of the myoblast differentiation markers myogenin and eMyHC (56.9% and 40.2% decrease in PD, respectively. p<0.01), whereas CGP had the opposite effects. siRNA mediated AT2R knockdown in mouse primary myoblasts suppressed the increase of myogenin and desmin, resulting in lowered differentiation. We analyzed changes in phosphoprotein levels in myoblasts after AT2R knockdown by phosphoprotein array and identified multiple changes, including increased phospho-ERK1/2 levels. Importantly, inhibition of ERK1/2 restored normal myoblast differentiation in the setting of AT2R knockdown, suggesting the AT2R positively regulates myoblast differentiation by reducing ERK1/2 activity. Furthermore, we found that skeletal muscle regeneration was reduced (decreased regenerating myofiber size and myogenin/desmin expression) in a mouse myocardial infarction model of CHF, concomitantly with markedly blunted increase of AT2R expression, strongly suggesting that the AT2R plays an important role in the reduction of skeletal muscle function in CHF. These data indicate that AT2R signaling positively regulates myoblast differentiation and potentiates skeletal muscle regeneration, providing a new therapeutic target in wasting disorders such as CHF and CKD.

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