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Oxidized low density lipoprotein‐induced transdifferentiation of bone marrow‐derived smooth muscle‐like cells into foam‐like cells in vitro
Author(s) -
Yu Jun,
Li Yan,
Li Mincai,
Qu Zhiling,
Ruan Qiurong
Publication year - 2010
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.1365-2613.2009.00693.x
Subject(s) - myocardin , transdifferentiation , microbiology and biotechnology , scavenger receptor , chemistry , vascular smooth muscle , myosin , bone marrow , biology , stem cell , lipoprotein , biochemistry , immunology , endocrinology , cholesterol , gene expression , smooth muscle , serum response factor , gene
Summary Oxidized‐low density lipoprotein (ox‐LDL) is believed to contribute to atherogenesis in part by being taken up into smooth muscle cells (SMC) via specific scavenger receptors; however, it is not clear whether ox‐LDL receptor(s) are expressed in bone marrow‐derived smooth muscle‐like cells (SMLCs) and whether they play a role in the process of SMLC development. Therefore, we examined the ox‐LDL‐induced transdifferentiation of SMLCs that is mediated by lectin‐like ox‐LDL receptor‐1 (LOX‐1). Smooth muscle progenitor cells (SMPCs) from bone marrow mesenchymal stem cells (BMSCs) were isolated using a tissue‐specific promoter sorting method with a mouse SM22_ promoter (_480 bp)/green fluorescent protein recombinant plasmid. The SMPCs were myocardin + CD105 + KDR + CD45 − CD34 − , but did not express SMC‐specific markers α‐smooth muscle actin (α‐SMA), SM22, smooth muscle myosin heavy chain (SM‐MHC) and smoothelin. After long‐term culture with platelet‐derived growth factor‐BB (PDGF‐BB), SMPCs expressed α‐SMA, SM22 and SM‐MHC and differentiated into SMLCs. When SMLCs were incubated with different concentrations of ox‐LDL, LOX‐1 expression on the surface of SMLCs gradually increased with the increase of the ox‐LDL concentration, but myocardin and SMC‐specific marker genes decreased, accordingly. Furthermore, receptor‐mediated endocytosis was enhanced and lipid droplets accumulated in the cytoplasm of SMLCs. A subpopulation of myocardin + CD105 + KDR + CD45 − CD34 − SMPCs exist in BMSCs that can differentiate into SMLCs under induction with PDGF‐BB. Moreover, LOX‐1 contributes to the ox‐LDL‐induced transdifferentiation of bone marrow‐derived SMLCs into foam‐like cells.