Abstract 029: Reduced Bone Marrow Adrenergic Receptor Signaling Modulates Inflammatory Factors and Alters Gut Microbiota
Brain - bone marrow (BM) communication is implicated in regulation of blood pressure (BP) in neurogenic hypertension (HTN), and chronic elevation of sympathetic drive contributes to BM inflammatory cell (IC) activity and promotes vascular inflammation. Our recent study linked gut dysbiosis to human and animal HTN; thus, we hypothesize that blocking the effects of sympathetic drive in the BM will result in reduction of BM ICs and modify gut microbiota. Methods: Whole BM cells were extracted from adrenergic receptor beta 1 and 2 knock out mice (Adrb1tm1BkkAdrb2tm1Bkk/J KO) and reconstituted into lethally- irradiated C57BL/6J mice to generate C57-AdrB1.B2 KO chimera, characterized by reduced/diminished effect of sympathetic drive on the BM cells. Control mice (C57-C57) were generated by reconstitution of irradiated C57BL/6J with whole BM from C57BL/6J mice. All mice were recovered for 2-3 months prior to measurements. Specific primers were used to amplify variable region 4-5 of 16S rDNA from isolated fecal DNA. Purified amplicons were pooled to generate bacterial library, quantified by qPCR and subjected to Illumina Miseq sequencing. Reads were aligned with the Silva nonredundant 16S reference database. BP recordings were performed using radiotelemetry (DSI). Blood was collected at Night (8-9pm, i.e. at highest activity) for analysis of circulating ICs. Results: We observed a significant reduction of circulating ICs (CD4+CD8+: 2.3±0.6% vs. 0.876±0.1%; CD11b+: 15.4±4% vs. 8.5±0.8%; CD184+CD62L+: 25±4.3% vs. 6.6±0.8%; (% of mononuclear cells)), and increase in endothelial progenitors (Tie2+: 21.3±1.5% vs. 32.2±5.7%) in chimera vs. control. A trend in BP reduction was observed in chimera (Day: 110±6 vs. 101±2 mm Hg; Night: 130±2 vs. 123±2 mm Hg). Expansion of Bacteroidetes (control: 34.2%±3.0 vs. chimera: 49.9%±3.3), and contraction of Firmicutes (control: 63.9%±3.0 vs. chimera: 48.9%±3.8) were observed in chimera, lowering the F/B ratio two fold. Conclusion: Diminished effect of BM sympathetic drive dampens BM-derived ICs and favors the bloom of Bacteroidetes phylum, suggesting the role of BM in gut homeostasis.
Author Disclosures: T. Yang: None. E. Li: None. N. Ahmari: None. J. Carvajal: None. M. Santisteban: None. S. Kim: None. M. Raizada: None. J. Zubcevic: None.
This research has received full or partial funding support from the American Heart Association, National Center.
- © 2015 by American Heart Association, Inc.