Role of human smooth muscle cell progenitors in atherosclerotic plaque development and composition.
OBJECTIVE
We analysed the possible protective role of human endothelial (EPCs) and smooth muscle (SPCs) progenitor cells on atherosclerosis development in apoE(-/-)RAG2(-/-) mice. We determined plasma levels of SPCs in coronary patients.


RESULTS
ApoE(-/-)RAG2(-/-) mice received four intravenous injections of saline, 5 x 10(5) SPCs, or 5 x 10(5) EPCs every other week, one (preventive approach) or 12(curative approach) weeks after starting a high fat diet. Derived-SPC levels were quantified from blood mononuclear cells of patients with stable angina (n = 10) and acute coronary syndromes (ACS, n = 9). SPCs reduced atherosclerosis development by 42% (P < 0.001), but had no effect on lesion progression. In the SPC group, collagen and smooth muscle cell content were increased (+80%, P < 0.001, +46%, P < 0.05, respectively), and macrophage content was decreased (-41%, P < 0.05). In the curative approach, macrophage content decreased by 40.5% (P < 0.05) after SPC injection. EPC injection had no effect on atherosclerosis development or progression. Peripheral blood-derived SPC levels were reduced in patients with ACS compared with stable angina patients (P < 0.05).


CONCLUSIONS
We demonstrate that SPCs limit plaque development and promote changes in plaque composition towards a stable phenotype in mice. Our finding in patients suggests that reduced peripheral blood-derived SPC levels might represent a mechanism contributing to plaque destabilization.
Zoll
Joffrey
J
INSERM U689, Hôpital Lariboisière, 41, Bd de la Chapelle, 75010 Paris, France.
Fontaine
Vincent
V
Gourdy
Pierre
P
Barateau
Veronique
V
Vilar
Jose
J
Leroyer
Aurelie
A
Lopes-Kam
Izolina
I
Mallat
Ziad
Z
Arnal
Jean-Francois
JF
Henry
Patrick
P
Tobelem
Gerard
G
Tedgui
Alain
A
D000368:Aged; D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002469:Cell Separation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D018450:Disease Progression; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology*
D001057:Apolipoproteins E; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse