Abstract P140: Myeloid Activation in Hypertension and Effects on Bone: A New End Organ?

Abstract

Hypertension affects approximately one-half of the adult population. Another common disease is osteoporosis, which affects 53 million people in the United States. Clinical studies have shown an association between hypertension and bone loss. We hypothesized that experimental hypertension would be associated with osteoporosis. In Angiotensin (Ang) II-induced hypertension, there is an increase in hematopoietic stem cells (HSCs) expressing the master myeloid transcription factor PU.1 (2.99 ± 0.92) vs. sham (0.17 ± 0.04,p=0.007). Here we reported an increase an osteoclasts number per mm 2 by Tartrate-resistant acid phosphatase staining in DOCA-salt hypertension (27.4 ± 2.3) vs. sham (12.09 ± 1.7, p=0.0002). Using microCT analysis of femoral bone, we found that Ang II-induced hypertension caused striking bone loss as reflected by decreases in cortical bone area, cortical thickness and trabecular number (see Table). We also examined bone strength using a three-point biomechanical testing. In keeping with the micro-CT data, both forms of hypertension were associated with increased bone fragility, reflected by several parameters including maximum force to failure and rigidity (see Table). Recent studies have implicated T cells in the genesis of osteoporosis, and in keeping with this, we found almost two-fold increase in both CD4 + and CD8 + T cells in the marrow of mice with DOCA-salt hypertension. Thus, in two models of experimental hypertension there is marked bone loss and the development of bone fragility, potentially related to T cell accumulation and cytokine release. These findings might explain the association between osteoporosis and hypertension.