LDL-cholesterol drives reversible myelomonocytic skewing in human bone marrow

This editorial refers to ‘Impact of cholesterol on proinflammatory monocyte production by the bone marrow’, by L.C.A. Stiekema et al., https://doi.org/10.1093/eurheartj/ehab465. In this issue of the European Heart Journal, Stiekema et al.1 show a dual proinflammatory role for plasma LDL-cholesterol (LDL-C) levels in haematopoietic stem and progenitor cells (HSPCs) from human bone marrow (BM). LDL-C promoted myelomonocytic skewing in BM HSPCs, driving monocyte production and a monocyte inflammatory signature. A maximum tolerated dose of cholesterol-lowering therapies (LDL-C reduction ∼66%) in familial hypercholesterolaemia (FH) patients reversed myelomonocytic skewing in BM HSPCs but not the monocyte inflammatory signature. Altogether, these findings provide the first genetic evidence for the involvement of LDL-C in myelomonocytic skewing in human HSPCs and reveal how LDL-C ties chronic inflammation to cardiovascular diseases (CVD) (Graphical Abstract). It is well established that monocytosis, the expansion of blood monocytes, is associated...