title: Overexpressed PLTP in macrophage may promote cholesterol accumulation by prolonged endoplasmic reticulum stress.
abstract: It is well known that phospholipid transfer protein (PLTP) is involved in the lipid metabolism and development of atherosclerosis (AS). Abundant PLTP is considered to be expressed on the foam cells derived from monocyte/macrophages in atherosclerotic plaques, suggesting that high level of active PLTP may promote the formation of foam cells. However, the exact role of PLTP on the process of macrophage derived foam cell formation remains unclear. The accumulation of free cholesterol (FC) in the cytoplasm may lead to the prolonged endoplasmic reticulum stress (ERs) and the imbalance of intracellular cholesterol homeostasis. Different PLTP level definitely alternates the phospholipids (PL) and cholesterol level in plasma, strongly suggesting that active PLTP may change the level of FC and PL intracellularly, which subsequently induced the ERs in macrophage. Thus, we hypothesize that high level of PLTP may promote the accumulation of cholesterol in macrophage via the alteration ratio of FC to PL. Therefore, validating this hypothesis may clarify the role of PLTP in macrophage ERs in AS and also raise a novel strategy in the regression of AS plaques via restoring intracellular membrane lipid homeostasis and attenuating ERs.
authors.affiliation: Department of Cardiology, Xiangya Second Hospital of Central South University, Changsha, China; Medical Research Centre, Northern Jiangsu People's Hospital, Yangzhou, China.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Medical Research Centre, Northern Jiangsu People's Hospital, Yangzhou, China. Electronic address: daxinw2002@sina.com.
authors.forename: Daxin
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China. Electronic address: shucunqin@hotmail.com.
authors.forename: Shucun
authors.initials: S
authors.lastname: Qin
mesh_terms: D000818:Animals; D050197:Atherosclerosis; D002784:Cholesterol / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D005487:Foam Cells / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D006949:Hyperlipidemias / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008962:Models, Theoretical; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C493430:PLTP protein, human; D049294:Phospholipid Transfer Proteins; C510091:phospholipid transfer protein, mouse; D002784:Cholesterol
keywords: Cholesterol accumulation; Endoplasmic reticulum stress; Free cholesterol; PLTP; Phospholipids