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 neuro-immune and immuno-metabolic 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.

Increased ROS production and DNA damage in monocytes are biomarkers of aging and atherosclerosis

“…In the present study we observed an increased peripheral monocytosis in apoE −/− mice and this finding is in agreement with other studies [29–32]. Previous studies suggest that hypercholesterolemia during aging may be associated with a homeostasis disruption in bone marrow [28, 33–38], leading to an increased entry of monocytes into atherosclerotic plaque [28, 39, 40]. In addition, previous reports revealed that hypercholesterolemia increased the expression of growth factors [41] and that, in this regard, apoE acts to regulate the proliferation of hematopoietic stem/progenitor cells leading to a subsequent expansion of myeloid lineage [28].…”

Neuroinflammation at the interface of depression and cardiovascular disease: Evidence from rodent models of social stress

“…These agents generally function to reduce inflammation by blocking the expression of inflammatory progenitors (NF-κB: Zhu et al., 2015; COX-2, iNOS: Li et al., 2015), but have also been shown to increase the amount of serotonin and norepinephrine available in the brain (Xu et al., 2010, Ahmed et al., 2014, Ji et al., 2014, Zhu et al., 2015). It should also be noted that diet and exercise can significantly influence the immune system and therefore lifestyle changes may also be useful therapy for inflammation-related psychiatric disorders and cardiovascular disease (reviewed in Nahrendorf and Swirski, 2015). Based on these findings, natural therapies with anti-inflammatory efficacy may represent a useful alternative therapeutic or adjuvant for depressed patients who present with elevated inflammation and may likely reduce CVD risk.…”

The predictive role of health‐promoting behaviours and perceived stress in aneurysmal rupture

“…Our findings suggest that higher perceived stress was significantly and independently associated with risk of aneurysmal rupture. As possible biological mechanisms underlying the association, it may be that stress (i) causes a surge in blood pressure that contributes to vascular events (Aggarwal et al., ); (ii) activates the hypothalamic–pituitary–adrenal axis, leading to changes in glucocorticoid secretion and increases in circulating catecholamines that collectively and progressively result in vascular endothelial dysfunction (Everson‐Rose et al., ; Poitras & Pyke, ); and (iii) affects the inflammatory pathway in a way that may lead to vascular wall injury (Chalouhi et al., ; Nahrendorf & Swirski, ). Although we did not examine specific mechanistic pathways, these possibilities are plausible because the mechanisms have been proposed to explain the relationship of psychological stress with many other vascular diseases such as stroke that have common features in terms of vascular damage.…”