Abstract P057: Is Hypertension a Disease of the Bone Marrow?
Decades of evidence have implicated involvement of inflammation in the development and establishment of hypertension (HTN); however, the central mechanisms remain elusive. We propose a hypothesis that dysfunctional bone marrow (BM) activity is critical in HTN, in view of the fact that BM is the predominant source of inflammatory and angiogenic cells. We provide the following evidence in support of this hypothesis: (1) BM from animal models of HTN is proinflammatory. Ablation of the spontaneously hypertensive rat (SHR) BM, and reconstitution with BM from the normotensive Wistar Kyoto (WKY), results in significant reduction in mean arterial pressure (MAP), as well as the decrease in proinflammatory and increase in angiogenic cells in the chimeric SHR; (2) Oral minocycline treatment attenuates MAP, restores autonomic balance, and decreases inflammation in both the SHR and Ang II rat HTN models; (3) Sympathetic nerve activity (SNA) and norepinephrine levels in the BM of the SHR and Ang II rat HTN models are elevated compared to normotensive rats; (4) C57-AdrB1.B2 knock-out (KO) chimera, generated by reconstitution of irradiated C57BL/6J mice with the BM cells of the adrenergic receptor beta 1/2 KO mice (Adrb1tm1Bkk Adrb2tm1Bkk/J), exhibits reduced peripheral inflammatory cell counts. Furthermore, transcriptomics analysis of the BM cells from these chimeric mice revealed significant changes in 67 signaling pathways, thirty-five of which were directly related to modulation of different immune system responses (P<0.01). Most notable were changes in the pathways involved in activation and migration of monocytes and T lymphocytes. These observations demonstrate that BM plays a critical role in regulation of the inflammatory status, and support our hypothesis that dysfunctional BM activity may be an important aspect in the development and establishment of HTN. AHA14SDG18300010.
Author Disclosures: J. Zubcevic: None. M.M. Santisteban: None. N. Ahmari: None. J.T. Schmidt: None. C.J. Martyniuk: None. J. Marulanda Carvajal: None. S. Kim: None. M.K. Raizada: None.
This research has received full or partial funding support from the American Heart Association, National Center.
- © 2015 by American Heart Association, Inc.