Abstract P160: Hypertension is Associated With Monocytes Activation in the Blood in Mice and Humans

Abstract

Monocytes play a crucial role in immune activation and the development of hypertension. Deletion of monocytes prevents experimental hypertension, and monocyte derived dendritic cells (DCs) and macrophages promote T cell activation and tissue damage. Our group recently found that monocytes exposed to hypertensive mechanical stretch convert to a pro-inflammatory phenotype denoted by expression CD14 + CD16 + , also known as intermediate monocytes. We aimed to determine whether hypertension has a direct effect on the bone marrow to activate the production and mobilization of monocytes. To study this, we initially analyzed the circulating monocytes from 15 normotensive and 12 hypertensive subjects using flow cytometry and found that hypertensive subjects have an absolute monocytosis compared to normotensives (1014 ± 113 vs. 567.5 ± 97 per uL, p < 0.05). This is associated with high numbers in both the classical CD14 + CD16 - monocytes and the non-classical CD14 low CD16 + monocytes. To further study mechanisms involved, we analyzed monocytes in the blood and bone marrow from C57BL/6 mice following two weeks of sham or Ang II infusion (490 ng/kg/min, s.c.). Similar to the findings in humans, more total monocytes were found in mice with Ang II-induced hypertension (46.7±10.1 vs 18.7±4.7 per μL, p<0.05). Ang II also induced an increase in Ly6C high expressing monocytes (Ang II: 34.1±65.6 vs. Sham: 12.3±3.5 per μL, p<0.05), reflecting activation. We also observed an increase in Ly6C high expressing monocytes in the bone marrow. Taken together, our results suggest that hypertension is associated with monocytosis in humans and mice, and this is likely due to increased BM production. This increase in monocytes may prime the immune system for activation and increased tissue inflammation. Moreover, the level of circulating monocytes might prove to be a useful biomarker of inflammation in hypertension.