A comprehensive mirnome analysis of macrophages isolated from db/db mice and selected mirnas involved in metabolic syndrome-associated cardiac remodeling

Abstract

Cardiac macrophages are known from various activities, therefore we presume that mi-croRNAs (miRNAs) produced or released by macrophages in cardiac tissue have impact on myo-cardial remodeling in individuals with metabolic syndrome (MetS). We aim to assess the cardiac macrophage miRNA profile by selecting those miRNA molecules that potentially exhibit regulatory functions in MetS-related cardiac remodeling. Cardiac tissue macrophages from control and db/db mice (an animal model of MetS) were counted and sorted with flow cytometry, which yielded two populations: CD45+CD11b+CD64+Ly6Chi and CD45+CD11b+CD64+Ly6Clow . Total RNA was then iso-lated, and miRNA expression profiles were evaluated with Next Generation Sequencing. We successfully sequenced 1400 miRNAs in both macrophage populations: CD45+CD11b+CD64+Ly6Chi and CD45+CD11b+CD64+Ly6Clow . Among the 1400 miRNAs, about 150 showed different expression levels in control and db/db mice and between these two subpopulations. At least 15 miRNAs are pos-sibly associated with MetS pathology in cardiac tissue due to direct or indirect regulation of the expression of miRNAs for proteins involved in angiogenesis, fibrosis, or inflammation. In this pa-per, for the first time we describe the miRNA transcription profile in two distinct macrophage populations in MetS-affected cardiac tissue. Although the results are preliminary, the presented data provide a foundation for further studies on intercellular cross-talk/molecular mechanism(s) involved in the regulation of MetS-related cardiac remodeling.