PLX224064

GSE144098: Sexual Dimorphism in Cardiac Transcriptome Associated with a Troponin C Murine Model of Hypertrophic Cardiomyopathy

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Heart disease remains the number one killer of women in the US. Nonetheless, studies in women and female animal models continue to be underrepresented in cardiac research. Hypertrophic cardiomyopathy (HCM), the most commonly inherited cardiac disorder, has been tied to sarcomeric protein variants. Among the susceptible genes, TNNC1encoding cardiac troponin C (cTnC)has contributed to a substantial HCM phenotype in mice. In this study we sought to characterize the sexual dimorphism observed within cardiac physiology and transcriptomics of adult male and female mice bearing the HCM-associated cTnC-A8V point mutation. The HCM mice showed a significant decrease in stroke volume, left ventricular diameter, volume, and relative wall thickness. Importantly, isovolumetric contraction time was significantly higher for female HCM mice. RNA sequencing revealed several altered canonical pathways within the HCM mice vs WT groups including an increase in EIF2 signaling, ILK signaling, actin nucleation by ARP-WASP complex, regulation of actin-based motility by Rho, VDR/RXR activation, and glutathione redox reactions pathways. In contrast, Valine Degradation, TCA Cycle II, Methionine Degradation, and Inositol Phosphate Compound pathways were notably down regulated in HCM mice. HCM male vs. female mice followed similar trends of the canonical pathways altered between the HCM and WT. Interestingly, seven of the genes that were differentially expressed in both the WT and HCM male vs female comparisons changed directions in fold change between the sexes. These data suggest a sexually-dimorphic HCM phenotype and identify several key pathways and genes that could be critical to sex differences seen in disease manifestation. SOURCE: Cynthia Vied (cynthia.vied@med.fsu.edu) - Florida State University