Cardiovascular Research Advance Access [Accepted Manuscript] published online on October 7, 2007
Cardiovascular Research, doi:10.1093/cvr/cvm034
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Role of human smooth muscle cell progenitors in atherosclerotic plaque development and composition
1 INSERM U689, Hôpital Lariboisière, 75010 Paris, France
2 INSERM U589, Institut L. Bugnard, CHU Rangueil, 31403 Toulouse, France
3 Service de Cardiologie (P.H.), Hôpital Lariboisière, Paris, France
4 Institut des Vaisseaux et du Sang, Hopital Lariboisiere, Paris, France
Corresponding Author: Alain Tedgui, PhD INSERM U689, Hôpital Lariboisière, 41, Bd de la Chapelle, 75010 Paris, France. Tel : 33-1-53216695; Fax : 33-1-42813128 E-mail : Tedgui{at}larib.inserm.fr
Aims: 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.
Methods and Results: ApoE-/-RAG2-/- mice received 4 intravenous injections of saline, 5·105 SPCs, or 5·105 EPCs every other week, one (preventive approach) or twelve (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.
KEYWORDS Vascular progenitor cells; cell therapy; atherosclerosis; coronary syndrome
Time for primary review: 18 days
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