Cardiac remodeling in feline hypertrophic cardiomyopathy (HCM) is poorly understood. To investigate underlying molecular mechanisms, we determined microRNA–mRNA interactions, regulatory networks, and upstream regulators using left ventricle (LV) and left atrium (LA) mRNA and microRNA sequencing datasets from cats with HCM and controls. Upstream regulators, molecules, and pathways associated with ischemia, inflammation, fibrosis, and cellular changes were observed in the HCM heart. In both the HCM LV and LA, TNFα, IL1β, and TGFβ were identified as upstream regulators, along with FGF23, THBS4, and FAMB177 as the top increased molecules. Relevant microRNAs included upstream regulator miR-132, enriched miR-124-3p, miR-122b-3p, miR-146-5p (HCM LV and LA), miR-370, miR-1185-5p, miR-12194-3p (HCM LV), miR-153-3p, miR-185-5p, and miR-185-3p (HCM LA). Macrophage pathways were activated, and granulocyte and agranulocyte adhesion and diapedesis were the most connected pathways. The HIF1α signaling pathway in the HCM LV, upstream regulators miR-1-3p and miR-204, and reduced miR-29 and miR-122-5p suggest cardioprotective mechanisms. Observed in the healthy heart and suspected to be involved in cardiac homeostasis were upstream regulators miR-96, inhibited WNT3A and miR-145, as well as miR-140-5p, miR-141-3p, miR-208b-3p, and miR-885-3p. This study provides further insights into the pathogenesis of HCM, and identifies the factors involved in the maintenance of a healthy LV and LA.

Hypertrophic cardiomyopathy (HCM) is the most prevalent acquired heart disease in cats and shares many clinical, phenotypical and pathological features with human HCM. Despite its relevance, knowledge on the pathomechanisms underlying the disease is limited. The present study aimed to characterize the molecular phenotypic changes in cardiomyocytes in feline HCM (fHCM) to better understand their contribution to the pathogenesis. To achieve this, the myocardium of the left ventricular free wall of 15 cats with confirmed fHCM and 30 control cats (two age groups: 16 cats 18-month-old, and 14 older adult cats without cardiac disease) were subjected to RT-qPCRs for markers representative of cardiomyocyte function. Overall, all markers were expressed at the highest level in young control cats, and increasing age correlated with decreased expression, regardless of sex. The comparison between the older adult control cats and those with HCM showed increased transcription levels for most markers associated with the disease, and higher expression of all markers in affected male cats compared to females. The constitutive transcription of all markers provides evidence of continuous myocardial adaptation throughout cats’ life. The high transcription values in the myocardium of young healthy cats and male cats affected by HCM suggest a particularly high myocardial responsiveness early in life and with HCM and reveal sex as relevant factor in the disease process. These results support the relevance of age and sex in the cardiac response to HCM in feline hearts.