Hypercholesterolemia Tunes Hematopoietic Stem/Progenitor Cells for Inflammation and Atherosclerosis

Area of Science:

• Cardiovascular biology
• Immunology
• Hematopoiesis

Background:

• Atherosclerosis, a chronic inflammatory disease, is the pathological basis of cardiovascular disease (CVD).
• Hypercholesterolemia is a significant independent risk factor for CVD, linked to myeloid cell expansion and accelerated atherosclerosis.
• Hematopoietic stem/progenitor cells (HSPCs) in bone marrow play a role in cholesterol homeostasis and are affected by hypercholesterolemia.

Purpose of the Study:

• To review the multifaceted mechanisms by which hypercholesterolemia influences HSPC activation, proliferation, differentiation, and mobilization.
• To explore how hypercholesterolemia modifies the bone marrow microenvironment, impacting HSPCs.
• To highlight potential therapeutic targets for controlling HSPC expansion and inflammation in CVD treatment.

Main Methods:

• Review of accumulated studies on hypercholesterolemia, atherosclerosis, and HSPC behavior.
• Analysis of the role of lipoprotein receptors in HSPC cholesterol homeostasis.
• Investigation into the effects of cholesterol reduction and reactive oxygen species inhibition on HSPCs.

Main Results:

• Hypercholesterolemia leads to HSPC expansion and differentiation due to impaired cholesterol efflux.
• Infusion of high-density lipoprotein (HDL) or apolipoprotein A-I (apoA-I) reverses hypercholesterolemia-induced HSPC expansion.
• Inhibition of reactive oxygen species production suppresses HSPC activation and leukocytosis, indicating multifactorial mechanisms.

Conclusions:

• Hypercholesterolemia directly and indirectly (via bone marrow microenvironment modification) evokes HSPC activation and mobilization.
• Understanding these mechanisms is crucial for developing novel therapeutic strategies targeting HSPC expansion and inflammation in CVD.
• Targeting key molecules involved in HSPC regulation may offer new avenues for treating cardiovascular disease.