title: A critical review of clinical arteriogenesis research.
abstract: In human hearts, an extensive pre-existing collateral network is present. This was shown unequivocally some 50 years ago in a series of very detailed post-mortem angiographic studies. In these studies, it was also observed that the pre-existent collateral vessels enlarge upon closure of an epicardial coronary artery, resulting in large collateral conduit arteries, in sharp contrast to earlier claims that human coronary arteries are functional end arteries. These insights still form the basis for the concept of arteriogenesis as positive remodeling of pre-existent arteriolar connections. Subsequent experimental studies disclosed the putative role of circulating cells, especially monocytes, which invade the proliferating vessel wall and secrete growth factors, degrading enzymes and survival factors that are required for the development of a mature collateral circulation. Experimental stimulation of arteriogenesis is feasible but to date a relatively low number of clinical studies, with no or limited success, have been performed. The use of intracoronary derived collateral flow index can increase the sensitivity to detect the effects of pharmacological compounds on arteriogenesis, which is important in first proof-of-principle studies. These invasive measurements also allow the detection of patients with an innate defect in their arteriogenic response to coronary obstruction. In a reversed bedside-to-bench approach, the characterization of ribonucleic acid and protein expression patterns in these patients generated new targets for therapeutic arteriogenesis.
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. n.vanroyen@amc.uva.nl
authors.forename: Niels
authors.initials: N
authors.lastname: van Royen
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schaper
authors.forename: William F
authors.initials: WF
authors.lastname: Fulton
mesh_terms: D000818:Animals; D003097:Collateral Circulation; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000502:physiology*; D006801:Humans; D018919:Neovascularization, Physiologic