Bone marrow-derived progenitor cells modulate vascular reendothelialization and neointimal formation: effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition.
OBJECTIVE
Atherosclerosis and restenosis after vascular injury are both characterized by endothelial dysfunction, apoptosis, inappropriate endothelialization, and neointimal formation. Bone marrow-derived endothelial progenitor cells have been implicated in neovascularization, resulting in adult blood vessel formation. Despite the anticipated stem cell plasticity, the role of bone marrow-derived endothelial progenitor cells has not been clarified in vascular lesion development.


RESULTS
We investigated vascular lesion formation in mice after transplantation of bone marrow transfected by means of retrovirus with enhanced green fluorescent protein. Carotid artery injury was induced, resulting in neointimal formation. Fluorescence microscopy and immunohistological analysis revealed that bone marrow-derived progenitor cells are involved in reendothelialization of the vascular lesions. Treatment with rosuvastatin (20 mg/kg body wt per day), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, enhanced the circulating pool of endothelial progenitor cells, propagated the advent of bone marrow-derived endothelial cells in the injured vessel wall, and, thereby, accelerated reendothelialization and significantly decreased neointimal formation.


CONCLUSIONS
Vascular lesion development initiated by endothelial cell damage is moderated by bone marrow-derived progenitor cells. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibition promotes bone marrow-dependent reendothelialization and diminishes vascular lesion development. These findings may help to establish novel pathophysiological concepts and therapeutic strategies in the treatment of various cardiovascular diseases.
Werner
Nikos
N
Medizinische Klinik und Poliklinik, Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.
Priller
Josef
J
Laufs
Ulrich
U
Endres
Matthias
M
Böhm
Michael
M
Dirnagl
Ulrich
U
Nickenig
Georg
G
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D016026:Bone Marrow Transplantation; D020212:Carotid Artery Injuries / Q000201:enzymology / Q000378:metabolism / Q000628:therapy; D002460:Cell Line; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D005464:Fluorobenzenes / Q000494:pharmacology; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011743:Pyrimidines; D012190:Retroviridae / Q000235:genetics; D000068718:Rosuvastatin Calcium; D033581:Stem Cell Transplantation; D013449:Sulfonamides; D017539:Tunica Intima / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008164:Luminescent Proteins; D011743:Pyrimidines; D013449:Sulfonamides; D049452:Green Fluorescent Proteins; D000068718:Rosuvastatin Calcium