title: Hypercholesterolemia Tunes Hematopoietic Stem/Progenitor Cells for Inflammation and Atherosclerosis.
abstract: As the pathological basis of cardiovascular disease (CVD), atherosclerosis is featured as a chronic inflammation. Hypercholesterolemia is an independent risk factor for CVD. Accumulated studies have shown that hypercholesterolemia is associated with myeloid cell expansion, which stimulates innate and adaptive immune responses, strengthens inflammation, and accelerates atherosclerosis progression. Hematopoietic stem/progenitor cells (HSPC) in bone marrow (BM) expresses a panel of lipoprotein receptors to control cholesterol homeostasis. Deficiency of these receptors abrogates cellular cholesterol efflux, resulting in HSPC proliferation and differentiation in hypercholesterolemic mice. Reduction of the cholesterol level in the lipid rafts by infusion of reconstituted high-density lipoprotein (HDL) or its major apolipoprotein, apoA-I, reverses hypercholesterolemia-induced HSPC expansion. Apart from impaired cholesterol metabolism, inhibition of reactive oxygen species production suppresses HSPC activation and leukocytosis. These data indicate that the mechanisms underlying the effects of hypercholesterolemia on HSPC proliferation and differentiation could be multifaceted. Furthermore, dyslipidemia also regulates HSPC-neighboring cells, resulting in HSPC mobilization. In the article, we review how hypercholesterolemia evokes HSPC activation and mobilization directly or via its modification of BM microenvironment. We hope this review will bring light to finding key molecules to control HSPC expansion, inflammation, and atherosclerosis for the treatment of CVD.
authors.affiliation: Beijing Key Laboratory of Diabetes Prevention and Research, Lu He Hospital, Capital Medical University, Beijing 101149, China. maxiaojuans@163.com.|Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing 101149, China. maxiaojuans@163.com.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Ma
authors.affiliation: Beijing Key Laboratory of Diabetes Prevention and Research, Lu He Hospital, Capital Medical University, Beijing 101149, China. yingmeif13@sina.com.|Department of Endocrinology, Lu He Hospital, Capital Medical University, Beijing 101149, China. yingmeif13@sina.com.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications* / Q000503:physiopathology; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D051379:Mice
keywords: atherosclerosis; cholesterol efflux; hematopoietic stem/progenitor cells; hypercholesterolemia; reactive oxygen species