Reverse remodeling and recovery from cachexia in rats with aldosteronism.
The congestive heart failure (CHF) syndrome with soft tissue wasting, or cachexia, has its pathophysiologic origins rooted in neurohormonal activation. Mechanical cardiocirculatory assistance reveals the potential for reverse remodeling and recovery from CHF, which has been attributed to device-based hemodynamic unloading whereas the influence of hormonal withdrawal remains uncertain. This study addresses the signaling pathways induced by chronic aldosteronism in normal heart and skeletal muscle at organ, cellular/subcellular, and molecular levels, together with their potential for recovery (Recov) after its withdrawal. Eight-week-old male Sprague-Dawley rats were examined at 4 wk of aldosterone/salt treatment (ALDOST) and following 4-wk Recov. Compared with untreated, age-/sex-/strain-matched controls, ALDOST was accompanied by 1) a failure to gain weight, reduced muscle mass with atrophy, and a heterogeneity in cardiomyocyte size across the ventricles, including hypertrophy and atrophy at sites of microscopic scarring; 2) increased cardiomyocyte and mitochondrial free Ca(2+), coupled to oxidative stress with increased H(2)O(2) production and 8-isoprostane content, and increased opening potential of the mitochondrial permeability transition pore; 3) differentially expressed genes reflecting proinflammatory myocardial and catabolic muscle phenotypes; and 4) reversal to or toward recovery of these responses with 4-wk Recov. Aldosteronism in rats is accompanied by cachexia and leads to an adverse remodeling of the heart and skeletal muscle at organ, cellular/subcellular, and molecular levels. However, evidence presented herein implicates that these tissues retain their inherent potential for recovery after complete hormone withdrawal.
Division of Cardiovascular Diseases, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Yaser
Y
Cheema
Wenyuan
W
Zhao
Tieqiang
T
Zhao
M Usman
MU
Khan
Kelly D
KD
Green
Robert A
RA
Ahokas
Ivan C
IC
Gerling
Syamal K
SK
Bhattacharya
Karl T
KT
Weber
D000818:Animals; D002100:Cachexia / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006861:Hydrogen Peroxide / Q000378:metabolism; D006929:Hyperaldosteronism / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009133:Muscular Atrophy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013997:Time Factors; D020257:Ventricular Remodeling
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D006861:Hydrogen Peroxide; D002118:Calcium