Transcriptional Response to Intermittent Hypoxia in the Heart of Germ‐Free Mice

Abstract

Accumulating evidence has demonstrated that the gut microbiota plays a critical role in health and disease and regulates the organismal response to environmental stresses. For example, we have found that intermittent hypoxia/hypercapnia (IHH), a condition mimicking obstructive sleep apnea in humans, induced significant alterations in gut microbiome/metabolism and enhanced atherogenesis and progression in two atherosclerosis mouse models (i.e., the LDLR−/− and ApoE−/− mice). Indeed, with a joint microbiome and metabolome analysis, we have determined that IHH‐induced remarkable compositional changes in both microbial (>10%, most remarkably in Clostridia) and metabolites (>22%) in the gut of LDLR−/− mice, which are tightly correlated with a significantly enhanced atherosclerotic lesion formation in pulmonary arteries and aorta. In the current project, in order to further understand the role of the microbiome in the cardiovascular response to hypoxia and/or hypercapnia, we developed a set up that allows the treatment of experimental mice with different levels of O2 and/or CO2 in a germ‐free environment. Using this experimental set up, we studied the impact of the microbiome on transcriptional response to intermittent hypoxia (IH) in the left ventricle of mouse heart. We identified modest but significant changes in gene expression in both conventionally reared and germ‐free mice under IH condition. We found 52 significantly altered genes (19 up‐regulated and 33 down‐regulated) in the conventional mice and 76 significantly altered genes (24 upregulated and 52 down‐regulated) in the germ‐free mice. In addition, we found that these significantly altered genes play important roles in the development and function of cardiomyocytes and endothelial cells. Interestingly, there were only 15 genes (2 up‐regulated and 13 down‐regulated) that were commonly altered in both conventional and germ‐free mice, representing 28% changes in conventional mice and 20% changes in germ‐free mice, respectively. In summary, we discovered that IH induces distinct transcriptional alterations between conventional and germ‐free mice, which demonstrates that microbiome plays a critical role in the transcriptional response to IH in the left ventricle of mouse heart.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.