In this study, we analyzed CD36 in 47 patients with HCM [29 with asymmetric septal hypertrophy (ASH) and 18 without ASH], 11 patients with dilated cardiomyopathy (DCM), and 26 patients with pressure-overload cardiac hypertrophy.
Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric septal hypertrophy and is often caused by mutations in MYBPC3 gene encoding cardiac myosin-binding protein C. In contrast to humans, who are already affected at the heterozygous state, mouse models develop the phenotype mainly at the homozygous state.
In this review paper, we elaborate on the pathophysiological differences between these two entities and highlight the disease-specific involvement of signaling molecules downstream of the Toll-like receptor 4, and the differential mechanism by which the inflammasome contributes to ASH versus NASH.
These data suggest an influence of the PNPLA3 polymorphism on the occurrence of HCC in patients with ASH/NASH but not among those with chronic viral hepatitis.
At the molecular level, ASH treatment was observed to restore the levels of BDNF and its receptor TRKB as well as the expression of other synaptic regulators, which are highly implicated in synaptic plasticity.
At the molecular level, ASH treatment was observed to restore the levels of BDNF and its receptor TRKB as well as the expression of other synaptic regulators, which are highly implicated in synaptic plasticity.
Mammalian target of rapamycin (or mechanistic target of rapamycin as it is known now (mTOR) and activated mTOR were significantly increased in chronic hepatitis C (HCV)-associated HCC, in HCC without a viral background, in alcoholic liver disease and Wilson disease. pPTEN, phosphatase and tensin homologue (PTEN) and pAKT showed a significant increase in HBV- and HCV-associated HCC, chronic hepatitis B, HCC without a viral background, alcoholic steatohepatitis (ASH) and Wilson disease.
Nonetheless, there are several disease-specific molecular signaling pathways, such as differential pathway activation downstream of TLR4 (MyD88-dependence in NASH versus MyD88-independence in ASH), inflammasome activation and IL-1β signaling in ASH, insulin resistance and lipotoxicity in NASH, and dysregulation of different microRNAs, which clearly highlight that ASH and NASH are two distinct biological entities.
Nonetheless, there are several disease-specific molecular signaling pathways, such as differential pathway activation downstream of TLR4 (MyD88-dependence in NASH versus MyD88-independence in ASH), inflammasome activation and IL-1β signaling in ASH, insulin resistance and lipotoxicity in NASH, and dysregulation of different microRNAs, which clearly highlight that ASH and NASH are two distinct biological entities.
Fresh human liver tissue was collected from ASH explant livers and HPC-enriched cell populations were obtained via four different isolation methods: side population (SP), epithelial cell adhesion molecule (EpCAM) and trophoblast antigen 2 (TROP-2) membrane marker isolation and laser capture microdissection.
Fresh human liver tissue was collected from ASH explant livers and HPC-enriched cell populations were obtained via four different isolation methods: side population (SP), epithelial cell adhesion molecule (EpCAM) and trophoblast antigen 2 (TROP-2) membrane marker isolation and laser capture microdissection.