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A. Al-Sharea et al.
blood pressure we focused on the specific role of b-2. Interestingly, a recent study by Mendez-Ferrer’s group has also highlighted the chronic role of nestin+ cells present in the BM and other tissues in regulating myeloid cell move- ment in the setting of atherosclerosis.44 Given that nestin+ cells in the BM express b-3 receptors and the data we have presented above regarding chronic sympathetic driven hypertension and its contribution to atherosclerosis, it is likely that this pathway may also play a role and warrants further investigation.
The obvious limitation of this study is that our findings were generated in mice. However, this also allowed us to isolate a prominent form of hypertension to reveal a novel atherogenic mechanism, which appears to be independent of endothelial dysfunction, and thus our findings also per- mit the current dogma to be challenged. While we revealed the effectiveness of propranolol in this model, there is a need to further investigate the effects of directly reducing enhanced hematopoiesis without targeting systemic blood
pressure. It is likely that with the development of anti- inflammatory drugs targeted at the hematopoietic system, it would be possible to dampen the effects on the hematopoietic system without affecting blood pressure which would hypothetically provide the same conclusions as in the present study. Finally, we only studied one form of hypertension, driven by sympathetic signaling. It would be of specific importance to extend a modified version of this hypothesis to hypertension driven by the RAS.
Funding
AJM is Career Development Fellow of the NHMRC (APP1085752) and a Future Leader Fellowship from the National Heart Foundation (100440) and a recipient of a CSL Centenary Award. This study was also supported by NHMRC project grants (APP1106154 and APP1142938) to AJM. and J.C-D. M.J.K is a Russell Berrie Foundation Scholar in Diabetes Research from the Naomi Berrie Diabetes Centre. PRN was sup- ported by grants from the NIH (R01HL1379 & R00HL1225).
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