It has been proposed that bone marrow contributes to the pathogenesis of arteriosclerosis. Nerve growth factor receptor (NGFR) is expressed in bone marrow stromal cells; it is also present in peripheral blood and ischemic coronary arteries. We hypothesized that bone marrow-derived NGFR-positive (NGFR+) cells regulate arterial remodeling. We found that human NGFR+ mononuclear cells (MNCs) in peripheral blood expressed markers for plasmacytoid dendritic cells (DCs) and were susceptible to apoptosis in response to proNGF secreted by activated arterial smooth muscle cells (SMCs). Bone marrow-specific depletion of NGFR+ cells increased neointimal formation following arterial ligation in mice. Bone marrow-derived NGFR+ cells accumulated in the neointima and underwent apoptosis. In contrast, in a bone marrow-specific NGFR-knockout model, SMCs occupied the neointima with augmented proliferation. NGFR+ cells in the neointima promoted mannose receptor C-type 1-positive anti-inflammatory macrophage accumulation and secreted anti-inflammatory IL-10, thereby inhibiting SMC proliferation in the neointima. In patients with acute coronary syndrome (ACS), NGFR+ peripheral MNCs increased after ACS onset. Multiple linear regression analysis showed that an insufficient increase in NGFR+ peripheral MNCs in ACS was an adjusted independent risk factor for 9-mo intimal progression of a nontargeted lesion. Taken together, these observations imply that bone marrow-derived NGFR+ DCs are suppressors of arteriosclerosis.NEW & NOTEWORTHY We propose a new concept of arterial remodeling after injury in which bone marrow-derived NGFR+ dendritic cells inhibit neointimal progression mediated by apoptosis. NGFR+ dendritic cells promote anti-inflammatory MRC1+ M2 macrophage accumulation and production of interleukin-10, inhibiting smooth muscle cell proliferation within the neointima. In a clinical study, insufficient mobilization of NGFR+ peripheral mononuclear cells in acute coronary syndrome was an independent risk factor for 9-mo nontargeted coronary intimal progression.
Keywords: apoptosis; arterial remodeling; bone marrow; dendritic cells; nerve growth factor receptor.