The link between hematopoiesis and atherosclerosis

REPROGRAM Principal Investigators working at Amsterdam University Medical Center and Ludwig Maximilians University, Munich published their expert comments on the link between hematopoiesis and atherosclerosis, based on the following article “AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate” in Science. 2019. 

There is mounting evidence that atherosclerosis is driven not just by dyslipidemia but also by inflammation. Experimental studies have repeatedly proved that inflammation has a role in atherosclerosis, and the Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS) provided clinical data showing that inflammation is an important driver of atherosclerotic cardiovascular disease.  Inflammation in atherosclerosis is manifested by an increased presence of immune cells and inflammatory mediators in the atherosclerotic plaque, arterial wall, and lymphoid tissues, as well as in the circulation. Several studies have shown that the systemic proinflammatory condition in cardiovascular disease originates at an early stage of hematopoiesis in the hematopoietic stem and progenitor cells (HSPCs) that eventually differentiate into and renew the myeloid-cell,lymphoid- cell, and erythroid-cell lineages of the bone marrow.

A direct link between dyslipidemia and HSPC activation has been reported. Hypercholesterolemia causes HSPCs to proliferate, leading to leukocytosis and atherosclerosis in both animal models and humans. In fact, studies have indicated an appreciable regulatory role for cholesterol efflux pathways in the mobilization of HSPCs from the bone marrow. Gu and colleagues recently reported in Science on some molecular determinants underlying this link. Overall, Gu et al. have uncovered a cholesterol metabolism pathway governing HSPC emergence in the development as well as in the expansion of the numbers of HSPCs in hypercholesterolemia. More data and comments on the work by this group can be found in the full article:

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement N°667837.