Surface markers of heterogeneous peripheral blood-derived smooth muscle progenitor cells.
OBJECTIVE
Smooth muscle progenitor cells (SMPCs) were intriguingly shown to act as a double-edged sword in the pathogenesis of atherosclerosis. To fully clarify the roles of SMPCs in atherosclerosis, a distinct panel of SMPC surface markers is mandatory to be developed.


RESULTS
Microarray gene expression analyses were used to discover potential surface markers of SMPCs. In vitro and in vivo experiments documented that platelet-derived growth factor receptor-β, carboxypeptidase M, carbonic anhydrase 12, receptor activity-modifying protein 1, and low-density lipoprotein receptor-related protein were the 5 specific surface markers regulating various SMPC functions, including migration, extracellular matrix formation, resistance to hypoxia, and anti-inflammation. In severe combined immunodeficiency/nonobese diabetic mice after femoral arterial wire injury, injected human peripheral blood mononuclear cells contributed to substantial amount of neointimal α-smooth muscle actin-positive cells, coexpressing platelet-derived growth factor receptor-β, carboxypeptidase M, carbonic anhydrase 12, receptor activity-modifying protein 1, and low-density lipoprotein receptor-related protein. Based on these markers, a novel quantification assay was developed to enumerate circulating early SMPC. Early SMPC numbers were higher in patients with unstable angina compared with those with normal coronary angiograms. In patients with acute ST-elevation myocardial infarction, different patterns of serial early SMPC changes were noted, related to different clinical presentations.


CONCLUSIONS
Surface markers of heterogeneous SMPCs exhibit various functions associated with atherosclerotic pathophysiology. Quantification of surface marker-defined SMPCs provides a platform for studying SMPCs in cardiovascular diseases.
Heart Failure Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222 Mai Chin Road, Keelung, Taiwan. bearty@adm.cgmh.org.tw
Chao-Hung
CH
Wang
Yun-Shien
YS
Lee
Shing-Jong
SJ
Lin
Hsiu-Fu
HF
Mei
Sheng-Yuan
SY
Lin
Min-Hui
MH
Liu
Jim-Ray
JR
Chen
Wen-Jin
WJ
Cherng
D000328:Adult; D050197:Atherosclerosis / Q000209:etiology; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000737:chemistry* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis; D013234:Stem Cells / Q000737:chemistry* / Q000502:physiology
D015415:Biomarkers; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D020797:Receptor, Platelet-Derived Growth Factor beta; D015740:Calcitonin Gene-Related Peptide