Surface markers of heterogeneous peripheral blood-derived smooth muscle progenitor cells.

Abstract

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.

METHODS AND 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.

• Authors: Chao-Hung Wang, Yun-Shien Lee, Shing-Jong Lin, Hsiu-Fu Mei, Sheng-Yuan Lin, Min-Hui Liu, Jim-Ray Chen, Wen-Jin Cherng
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 32 Issue 8 Pg. 1875-83 (Aug 2012) ISSN: 1524-4636 [Electronic] United States
• PMID: 22679308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• LRP1 protein, human
• Low Density Lipoprotein Receptor-Related Protein-1
• Receptor, Platelet-Derived Growth Factor beta
• Calcitonin Gene-Related Peptide

Topics

• Adult
• Atherosclerosis (etiology)
• Biomarkers (analysis)
• Blotting, Western
• Calcitonin Gene-Related Peptide (pharmacology)
• Cells, Cultured
• Endothelial Cells (cytology)
• Female
• Flow Cytometry
• Humans
• Immunohistochemistry
• Low Density Lipoprotein Receptor-Related Protein-1 (analysis)
• Male
• Middle Aged
• Myocytes, Smooth Muscle (chemistry, physiology)
• Oligonucleotide Array Sequence Analysis
• Phenotype
• Real-Time Polymerase Chain Reaction
• Receptor, Platelet-Derived Growth Factor beta (analysis)
• Stem Cells (chemistry, physiology)