Lifestyle effects on hematopoiesis and atherosclerosis

Abstract

Diet, exercise, stress, and sleep are receiving attention as environmental modifiers of chronic inflammatory diseases, including atherosclerosis, the culprit condition of myocardial infarction and stroke. Accumulating data indicate that psychosocial stress and a high-fat, high-cholesterol diet aggravate cardiovascular disease, whereas regular physical activity and healthy sleeping habits help prevent it. Here, we raise the possibility that inflammation-associated leukocyte production plays a causal role in lifestyle effects on atherosclerosis progression. Specifically, we explore whether and how potent real-life disease modifiers influence hematopoiesis' molecular and cellular machinery. Lifestyle, we hypothesize, may rearrange hematopoietic topography, diverting production from the bone marrow to the periphery, thus propagating a quantitative and qualitative drift of the macrophage supply chain. These changes may involve progenitor-extrinsic and intrinsic communication nodes that connect organ systems along neuroimmune and immunometabolic axes, ultimately leading to an altered number and phenotype of lesional macrophages. We propose that, in conjunction with improved public health policy, future therapeutics could aim to modulate the quantitative and qualitative output, as well as the location, of the hematopoietic tree to decrease the risk of atherosclerosis complications.

Keywords: atherosclerosis; bone marrow; cell proliferation; diet; hematopoiesis; macrophages; monocytes; psychosocial, stress; sleep; spleen.

Conflict of interest statement

Disclosure Section

The authors declare no conflict of interest.

© 2015 American Heart Association, Inc.

Figures

Figure 1

The hematopoietic tree and properties of myeloid progenitors as a function of their differentiation.

Figure 2

The hematopoietic niche. The cartoon depicts components that indirectly regulate the activity of hematopoietic stem cells. The upper panel on the left shows an original microscopy image of the mouse bone marrow, illustrating sympathetic nerve fibers traveling along bone marrow vessels. The lower left panel was obtained in the bone marrow of a mouse after ischemic stroke, and shows replicating hematopoietic progenitor cells (arrows). Both images are taken from Courties G. et. al..

Figure 3

The hematopoietic tree on the move. The cartoon illustrates the hypothetical contribution of life style factors towards shifting the macrophage supply peripherally and associating with atherosclerosis progression and complication.