Statin Therapy Accelerates Reendothelialization

Abstract

Background-Primary and secondary prevention trials suggest that statins possess favorable effects independent of cholesterol reduction. We investigated whether statin therapy may also accelerate reendothelialization after carotid balloon injury. Methods and Results-Simvastatin treatment in 34 male Sprague-Dawley rats accelerated reendothelialization of the balloon-injured arterial segments (reendothelialized area at 2 weeks, 12.3Ϯ1.8 versus 5.4Ϯ1.1 mm 2 , PϽ0.01) and resulted in a dose-dependent (0.2 or 1 mg/kg IP) significant reduction in neointimal thickening at 2, 3, and 4 weeks compared with saline-injected controls (nϭ18). To elucidate the mechanism, we investigated the contribution of bone marrow-derived endothelial progenitor cells (EPCs) by bone marrow transplantation from Tie2/lacZ mice to background mice or nude rats. X-gal staining of mouse carotid artery specimens revealed a 2.9-fold increase in the number of ␤-gal-positive cells per square millimeter appearing on the carotid artery luminal surface at 2 weeks, and double-fluorescence immunohistochemistry disclosed a significant 5-fold increase in the number of double-positive cells (␤-gal, isolectin B4) on the luminal surface in carotid arteries of statin-treated nude rats (20Ϯ3 versus 4Ϯ1 cells/mm surface length, PϽ0.005). Statins increased circulating rat EPCs (2.4-fold at 2 weeks and 2.5-fold at 4 weeks, PϽ0.001) and induced adhesiveness of cultured human EPCs by upregulation of the integrin subunits ␣ 5 , ␤ 1 , ␣ v , and ␤ 5 of human EPCs as shown by reverse transcription-polymerase chain reaction and fluorescence-activated cell sorting. Conclusions-These findings establish additional mechanisms by which statins may specifically preempt disordered vascular wall pathology and constitute physiological evidence that EPC mobilization represents a functionally relevant consequence of statin therapy.

Efficacy of Simvastatin in Bone Regeneration After Surgical Removal of Mandibular Third Molars: A Clinical Pilot Study

“…10 -8 M Simvastatin promoted osteogenic activity in vitro [39] Statins increase the number of circulating Endothelial Progenitor Cells (EPCs), accelerate re-endothelalization after carotid ballon myocardial surgery and improve postischemic cardiac function. Statins induce angiogenesis by promoting the proliferation, migration and survival of EPCs [40].…”

Neurorestorative treatment of stroke: Cell and pharmacological approaches

“…Many of the pleiotropic effects of statins are cholesterol independent, such as improvement of endothelial function, increased NO bioavailability, antioxidant properties, inhibition of inflammatory responses, immunomodulatory actions, upregulation of endothelial nitric oxide synthase (eNOS), decrease of platelet activation, and regulation of progenitor cells. 42,43 Pretreatment of stroke with statins reduces brain infarct size and improves neurological outcome by directly upregulating brain eNOS. 44,45 Combination atorvastatin and recombinant human tissue plasminogen activator (rhtPA) treatment 4 hours after stroke induces downregulation of tissue factor, protease-activated receptor 1, intercellular adhesion molecule 1, and matrix metalloproteinase 9 (MMP 9); concomitantly, it reduces cerebral microvascular thrombosis and enhances microvascular integrity.…”

Atorvastatin inhibits homocysteine-induced dysfunction and apoptosis in endothelial progenitor cells

“…Recent studies have suggested that endothelial progenitor cells (EPCs) may contribute to neovasculogenesis and reendothelialization of damaged blood vessels to maintain the endothelium [2,3] . Some cardiovascular diseases (CVD) and cardiovascular risk factors are associated with lower numbers and dysfunction of circulating EPCs [4][5][6] .…”