Myeloid cells regulate plasma LDL-cholesterol levels.

PURPOSE OF REVIEW

Leukocytosis, elevated blood leukocyte levels, is associated with enhanced cardiovascular risk in humans. Hematopoietic stem and progenitor cells (HSPCs) drive leukocyte production in a process called hematopoiesis, which mainly occurs in the bone marrow, and under certain conditions also in other organs such as the spleen. Cholesterol accumulation in HSPCs enhances hematopoiesis, increasing levels of blood monocytes that infiltrate into atherosclerotic plaques. Although HSPC proliferation and monocytosis enhance atherogenesis in several studies, concomitant decreases in LDL-cholesterol levels have also been reported, associated with anti-atherogenic effects. This review focuses on the link between HSPC proliferation, leukocytosis, plasma LDL-cholesterol levels, and atherogenesis.

RECENT FINDINGS

Recent studies have shown that an acute infection enhances cholesterol accumulation in HSPCs, driving HSPC proliferation, and leading to the expansion of myeloid cells (monocytes, neutrophils, and macrophages). Enhanced hematopoiesis is associated with low plasma LDL-cholesterol levels in animal models and humans, probably because of the increased number of myeloid cells that take up LDL-cholesterol. Despite low-plasma LDL-cholesterol levels, specific patient populations with enhanced hematopoiesis show increased cardiovascular risk.

SUMMARY

Enhanced hematopoiesis and monocytosis may accelerate atherogenesis. Studies on these processes may lead to the identification of new therapeutic targets for cardiovascular diseases.