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DOI: 10.1055/s-0037-1598978
Upregulation of Inflammatory Pathways in Mice with Hypertrophic Cardiomyopathy
Publication History
Publication Date:
02 February 2017 (online)
Objectives: To assess the role of hypoxia-induced transcription factor (HIFs) and reactive oxygen species (ROS) on disease progression in a hypertrophic cardiomyopathy mouse model.
Methods: Mice carrying the human Arg719Trp mutation in the α-cardiac myosin heavy chain gene (αMHC719/+) were compared with wildtypes (WT). Myocardial wall thickness was measured on M-mode in vivo echocardiographic imaging. RNA and protein expression of the myocardial HIF1α as well as components of the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase was assessed ex vivo by real-time polymerase chain reaction (RT-PCR) and by western blot, respectively. ROS production was measured by electron paramagnetic resonance.
Results: αMHC719/+ mice developed hypertrophic cardiomyopathy. Myocardial HIF1α expression was increased on both the RNA as well as the protein level in αMHC719/+ as compared with WT mice. There was an upregulation of p22phox, an essential component of the NADPH-oxidase, on a protein but not on the RNA-level in αMHC719/+ as compared with WT mice (see [Table 1]). αMHC719/+ mice showed an increase in relative ROS- and superoxide-generation.
Conclusion: Activation of HIFs and increased ROS production suggest the influence of inflammatory pathways on pathogenesis in a murine HCM mouse model. These results might offer new treatment targets in HCM.