Myostatin regulates skeletal muscle size via the activin receptor IIB (ActRIIB). However, its effect on muscle energy metabolism and energy-dependent muscle function remains largely unexplored. This question needs to be solved urgently since various therapies for neuromuscular diseases based on blockade of ActRIIB signaling are being developed. Here, we show in mice, that 4-month pharmacologica...

Circulating endothelin-1 (ET-1) levels are increased in cirrhosis. The liver is an important site for circulating ET-1 clearance through the ET(B) receptor. We evaluated ET-1 kinetics in cirrhosis to determine if a reduced liver clearance contributes to this process. Cirrhosis was induced by carbon tetrachloride in rats. Hepatic ET-1 clearance was measured in isolated perfused livers using the ...

The oxygen limitation theory states that capillarization of the sinusoidal endothelium in cirrhosis impairs hepatocellular oxygen uptake manifesting as a reduction in oxygen-dependent enzyme activity including phase 1 drug metabolism. The hepatic artery supplies highly oxygenated blood to the liver. Therefore, we tested whether augmentation of hepatic arterial blood flow could improve hepatic o...

Concomitant steatosis in chronic hepatitis C is associated with fibrosis and unfavorable treatment outcome. Central zone injury in nonalcoholic steatohepatitis (NASH) manifests as central portalization, with centrizonal microvessels and ductular reaction. We investigated whether central portalization in steatotic HCV biopsies would identify patients with metabolic risk factors for NASH. Liver b...

This study examined the effects of the intensity and duration of exercise on the nature and magnitude of training adaptations in muscle of adolescent (2-3 yr old) racehorses. Six thoroughbreds that had been pretrained for 2 mo performed six consecutive conditioning programs of varying lactate-guided intensities [velocities eliciting blood lactate concentrations of 2.5 mmol/l (v2.5) and 4 mmol/l...

Microvascular endothelial cells (ECs) are increasingly recognized as organ-specific gatekeepers of their microenvironment. Microvascular ECs instruct neighboring cells in their organ-specific vascular niches through angiocrine factors, which include secreted growth factors (angiokines), extracellular matrix molecules, and transmembrane proteins. However, the molecular regulators that drive orga...

Alterations in the liver microcirculation were characterized by use of the multiple-indicator dilution technique in 25 cirrhotic patients undergoing hemodynamic evaluation of portal hypertension. Hepatic vein outflow dilution curves were obtained after portal vein or hepatic artery injections of a vascular reference substance (labeled erythrocytes) and of diffusible substances (labeled albumin ...

Various indices of capillary supply to the rat heart were studied in neonatal rats injected for 2 or 4 weeks with protamine sulfate in saline (subcutaneously, 60 mg/kg body weight, 2 times/day). Cardiac capillarization was evaluated not only by traditional indices for the capillary supply, such as mean capillary density and myocyte-to-capillary ratio, but also by a more advanced morphometric me...

Activation of endogenous cardiac stem/progenitor cells (eCSCs) can improve cardiac repair after acute myocardial infarction. We studied whether the in situ activation of eCSCs by insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) could be increased using a newly developed hydrogel in chronic myocardial infarction (MI). One-month post-MI pigs underwent NOGA-guided intramyoca...

BACKGROUND & AIMS Liver fibrogenesis - scarring of the liver that can lead to cirrhosis and liver cancer - is characterized by hepatocyte impairment, capillarization of liver sinusoidal endothelial cells (LSECs) and hepatic stellate cell (HSC) activation. To date, the molecular determinants of a healthy human liver cell phenotype remain largely uncharacterized. Here, we assess the transcriptome...