Modifiable Cardiovascular Risk, Hematopoiesis, and Innate Immunity

Abstract

Unhealthy diet, lack of exercise, psychosocial stress, and insufficient sleep are increasingly prevalent modifiable risk factors for cardiovascular disease. Accumulating evidence indicates that these risk factors may fuel chronic inflammatory processes that are active in atherosclerosis and lead to myocardial infarction and stroke. In concert with hyperlipidemia, maladaptive immune system activities can contribute to disease progression and increase the probability of adverse events. In this review, we discuss recent insight into how the above modifiable risk factors influence innate immunity. Specifically, we focus on pathways that raise systemic myeloid cell numbers and modulate immune cell phenotypes, reviewing hematopoiesis, leukocyte trafficking, and innate immune cell accumulation in cardiovascular organs. Often, relevant mechanisms that begin with lifestyle choices and lead to cardiovascular events span multiple organ systems, including the central nervous, endocrine, metabolic, hematopoietic, immune and, finally, the cardiovascular system. We argue that deciphering such pathways provides not only support for preventive interventions but also opportunities to develop biomimetic immunomodulatory therapeutics that mitigate cardiovascular inflammation.

Keywords: arteriosclerosis; atherosclerosis; hematopoiesis; lifestyle; macrophages.

Fig. 1.. Lifestyle factors affect hematopoiesis in cardiovascular disease.

The cartoon illustrates the various pathways how lifestyle factors influence hematopoiesis and increase inflammatory leukocyte supply to the atherosclerotic lesion, accelerating its progression. CXCL indicates C-x-c chemokine ligand; CSF1, colony stimulating factor 1; HSPC, hematopoietic stem and progenitor cell. Cartoon summarizes data in references^{, , , , , ,} .

Fig. 2.. Sleep controls hematopoiesis and protects against atherosclerosis.

The cartoon illustrates how sleep influences hematopoiesis and moderates leukocyte supply to the atherosclerotic lesions. Sleep induces hypocretin release from the lateral hypothalamus, which circulates to the bone marrow and reduces CSF1 secretion from hypocretinreceptor-expressing pre-neutrophils. Sleep fragmentation leads to decreased release of hypocretin, heightening bone marrow CSF1 levels. CSF1 stimulates hematopoietic stem and progenitor cell proliferation, resulting in increased supply of inflammatory leukocytes. The cartoon was adapted from McAlpine et al. (ref). CSF1 indicates colony stimulating factor 1.

Fig. 3.. Interrelated pathways and modifiable risk factors for cardiovascular disease.

The cartoon depicts how physical activity may moderate innate immunity through multiple organs systems, ultimately affecting cardiovascular disease inception and progression.