Effect of Lipids and Lipoproteins on Hematopoietic Cell Metabolism and Commitment in Atherosclerosis

Abstract

Hematopoiesis is the process that leads to multiple leukocyte lineage generation within the bone marrow. This process is maintained throughout life thanks to a nonstochastic division of hematopoietic stem cells (HSCs), where during each division, one daughter cell retains pluripotency while the other differentiates into a restricted multipotent progenitor (MPP) that converts into mature, committed circulating cell. This process is tightly regulated at the level of cellular metabolism and the shift from anaerobic glycolysis, typical of quiescent HSC, to oxidative metabolism fosters HSCs proliferation and commitment. Systemic and local factors influencing metabolism alter HSCs balance under pathological conditions, with chronic metabolic and inflammatory diseases driving HSCs commitment toward activated blood immune cell subsets. This is the case of atherosclerosis, where impaired systemic lipid metabolism affects HSCs epigenetics that reflects into increased differentiation toward activated circulating subsets. Aim of this review is to discuss the impact of lipids and lipoproteins on HSCs pathophysiology, with a focus on the molecular mechanisms influencing cellular metabolism. A better understanding of these aspects will shed light on innovative strategies to target atherosclerosis-associated inflammation.