Low Molecular Mass Myocardial Hyaluronan in Human Hypertrophic Cardiomyopathy.
Christina E LorénChristen P DahlLan DoVibeke M AlmaasOdd R GeiranStellan MörnerUrban HellmanPublished in: Cells (2019)
During the development of hypertrophic cardiomyopathy, the heart returns to fetal energy metabolism where cells utilize more glucose instead of fatty acids as a source of energy. Metabolism of glucose can increase synthesis of the extracellular glycosaminoglycan hyaluronan, which has been shown to be involved in the development of cardiac hypertrophy and fibrosis. The aim of this study was to investigate hyaluronan metabolism in cardiac tissue from patients with hypertrophic cardiomyopathy in relation to cardiac growth. NMR and qRT-PCR analysis of human cardiac tissue from hypertrophic cardiomyopathy patients and healthy control hearts showed dysregulated glucose and hyaluronan metabolism in the patients. Gas phase electrophoresis revealed a higher amount of low molecular mass hyaluronan and larger cardiomyocytes in cardiac tissue from patients with hypertrophic cardiomyopathy. Histochemistry showed high concentrations of hyaluronan around individual cardiomyocytes in hearts from hypertrophic cardiomyopathy patients. Experimentally, we could also observe accumulation of low molecular mass hyaluronan in cardiac hypertrophy in a rat model. In conclusion, the development of hypertrophic cardiomyopathy with increased glucose metabolism affected both hyaluronan molecular mass and amount. The process of regulating cardiomyocyte size seems to involve fragmentation of hyaluronan.
Keyphrases
- hypertrophic cardiomyopathy
- left ventricular
- end stage renal disease
- heart failure
- chronic kidney disease
- ejection fraction
- newly diagnosed
- endothelial cells
- peritoneal dialysis
- type diabetes
- prognostic factors
- magnetic resonance
- fatty acid
- blood glucose
- skeletal muscle
- oxidative stress
- induced apoptosis
- metabolic syndrome
- signaling pathway
- patient reported outcomes
- insulin resistance
- adipose tissue
- patient reported
- induced pluripotent stem cells