title: Pharmacological approaches to improve endothelial repair mechanisms.
abstract: Endothelial injury is thought to play a pivotal role in the development and progression of vascular diseases, such as atherosclerosis, hypertension or restenosis, as well as their complications, including myocardial infarction or stroke. Accumulating evidence suggests that bone marrow-derived endothelial progenitor cells (EPCs) promote endothelial repair and contribute to ischemia-induced neovascularization. Coronary artery disease and its risk factors, such as diabetes, hypercholesterolemia, hypertension and smoking, are associated with a reduced number and impaired functional activity of circulating EPCs. Moreover, initial data suggest that reduced EPC levels are associated with endothelial dysfunction and an increased risk of cardiovascular events, compatible with the concept that impaired EPC-mediated vascular repair promotes progression of vascular disease. In this review we summarize recent data on the effects of pharmacological agents on mobilization and functional activity of EPCs. In particular, several experimental and clinical studies have suggested that statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, PPAR-gamma agonists and erythropoietin increase the number and functional activity of EPCs. The underlying mechanisms remain largely to be defined; however, they likely include activation of the PI3-kinase/Akt pathway and endothelial nitric oxide synthase, as well as inhibition of NAD(P)H oxidase activity of progenitor cells.
authors.affiliation: Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland. christian.besler@access.uzh.ch
authors.forename: Christian
authors.initials: C
authors.lastname: Besler
authors.forename: Carola
authors.initials: C
authors.lastname: Doerries
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giannotti
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
mesh_terms: D000071916:AC133 Antigen; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000494:pharmacology; D018952:Antigens, CD34 / Q000097:blood; D050197:Atherosclerosis / Q000503:physiopathology; D001578:Benzopyrans / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000503:physiopathology; D000077261:Carvedilol; D002454:Cell Differentiation; D003327:Coronary Disease / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000293:injuries*; D004921:Erythropoietin / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D000068577:Nebivolol; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists; D010455:Peptides / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects*; D012307:Risk Factors; D000077154:Rosiglitazone; D013234:Stem Cells / Q000187:drug effects*; D045162:Thiazolidinediones / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000071916:AC133 Antigen; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015703:Antigens, CD; D018952:Antigens, CD34; D001578:Benzopyrans; D002227:Carbazoles; D004983:Ethanolamines; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D010455:Peptides; D011412:Propanolamines; D011945:Receptors, Angiotensin; D045162:Thiazolidinediones; D014665:Vasodilator Agents; D000068577:Nebivolol; D000077154:Rosiglitazone; D000077261:Carvedilol; D004921:Erythropoietin