Sympathetic Nervous System

Abstract

Activation of the sympathetic nervous system after myocardial infarction results in the mobilization of hematopoietic stem cells, causing an inflammatory boost that accelerates atherosclerosis. This may have important implications for future therapeutic interventions targeting inflammatory pathways. The social and economic impacts of atherosclerosis and subsequent macrovascular clinical manifestations like myocardial infarction (MI) and stroke are immense. Complications of atherosclerosis and MI, such as heart failure, and also recurrent cardiovascular events present a major challenge. They seem to occur more frequently after MI than expected by presumed linear progression of atherosclerosis. In a recent article in Nature , Dutta et al1 found strong evidence that, like in a vicious cycle, acute MI itself accelerates atherosclerosis by triggering a burst of acute systemic inflammation initiated by progenitor cell mobilization from the bone marrow niche. The authors present 4 major findings: (1) acute MI (but also stroke) activates the sympathetic nervous system (SNS); (2) this causes the release of upstream progenitor cells from bone marrow niches; (3) these cells are hosted by the spleen leading to amplified extramedullary myelopoiesis; and (4) at the end of this multimodal cascade, there is a strong increase in inflammation in atherosclerotic plaques, leading to increased size and instability. The authors also show that experimental MI in apolipoprotein E–/– mice activates inflammatory pathways. In serial measurements after coronary ligation, concentrations of cathepsin in aortic plaques and the expression of the inflammatory cytokines interleukin (IL)-6, myeloperoxidase, and matrix metalloproteinase-9 were increased. Consecutively, this was associated with higher vulnerability of atherosclerotic plaque, as demonstrated by decreased thickness of the fibrous cap, and enlarged necrotic cores. Moreover, after MI, the number of macrophages and monocytes, especially the Ly-6Chigh monocyte subset, were increased in the aorta of apolipoprotein E–/– mice and exhibited higher levels of messenger …