Comparative proteomics profiling reveals role of smooth muscle progenitors in extracellular matrix production.
OBJECTIVE
Recent studies on cardiovascular progenitors have led to a new appreciation that paracrine factors may support the regeneration of damaged tissues.


RESULTS
We used a shotgun proteomics strategy to compare the secretome of peripheral blood-derived smooth muscle progenitors (SPCs) with human aortic smooth muscle cells. The late-outgrowth SPCs produced fewer proteolytic enzymes and inflammatory cytokines and showed reduced invasive capacity. Similar to smooth muscle cells, SPCs secreted extracellular matrix. However, SPCs produced different matrix proteins, as evidenced by the truncation of proangiogenic domains in collagen alpha-1 (I) and increased production of periostin. Moreover, SPCs retained serum proteins, including proteoglycans, regulating collagen assembly; and pigment epithelium-derived factor, a potent inhibitor of angiogenesis. As a functional consequence, their conditioned medium was less angiogenic, as demonstrated by endothelial tube formation assays in vitro and implantation of Matrigel plugs into nude, severe combined immunodeficient mice (NOD/SCID).


CONCLUSIONS
The present study represents an important conceptual development, suggesting that SPCs may contribute to extracellular matrix production.
Simper
David
D
Department of Cardiology, Phoenix VA Health Care System, Phoenix, AZ, USA.
Mayr
Ursula
U
Urbich
Carmen
C
Zampetaki
Anna
A
Prokopi
Marianna
M
Didangelos
Athanasios
A
Saje
Angelika
A
Mueller
Michael
M
Benbow
Ulrike
U
Newby
Andrew C
AC
Apweiler
Rolf
R
Rahman
Salman
S
Dimmeler
Stefanie
S
Xu
Qingbo
Q
Mayr
Manuel
M
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002478:Cells, Cultured; D056148:Chromatography, Reverse-Phase; D017077:Culture Media, Conditioned / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D010447:Peptide Hydrolases / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D013234:Stem Cells / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
D001798:Blood Proteins; D017077:Culture Media, Conditioned; D018836:Inflammation Mediators; D010447:Peptide Hydrolases