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 microRNAs (miRNAs) produced or released by macrophages in cardiac tissue have impact on myocardial 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 isolated, 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 possibly 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 paper, 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.