Therapeutic angiogenesis for myocardial ischemia revisited: basic biological concepts and focus on latest clinical trials

Abstract

Therapeutic angiogenesis is based on the premise that the development of new blood vessels can be augmented by exogenous administration of the appropriate growth factors. Over the last years, successful preclinical studies and promising results of early clinical trials have created great excitement about the potential of therapeutic angiogenesis for patients with advanced ischemic heart disease. The authors provide an overview of the biology of angiogenesis, the basic characteristics of angiogenic factors, and the different routes of their delivery. They discuss experimental studies in animal models of myocardial ischemia and outline available clinical studies on therapeutic angiogenesis for myocardial ischemia. Related safety issues are also addressed followed by a critical perspective about the future of proangiogenic therapies for ischemic cardiovascular disorders. Despite the established proof of concept and reasonable safety, however, results of the latest trials on therapeutic angiogenesis for myocardial ischemia have provided inconsistent results and the definite means of inducing clinically useful therapeutic angiogenesis remain elusive. More studies are required to gain further insights into the biology of angiogenesis and address pharmacological limitations of current approaches of angiogenic therapy. The authors hope and envisage that in the not-too-distant future, these investigative efforts will lead to important new strategies for treatment of myocardial ischemic syndromes. Means of non-invasive individualized pharmacological therapeutic neovascularization may be the next major advance in the treatment of ischaemic heart disease.

The Efficacy of Therapeutic Angiogenesis Using Basic Fibroblast Growth Factor in Patients With Coronary Artery Disease: A Double-Blind, Placebo-Controlled Study

“…3 Another concern regarding the use of FGF-2 is its safety due to its probable side effects, including acute severe hypotension and renal insufficiency. 16,36 According to the previous studies, single local administration of FGF-2 seems to be well-tolerated and safe. 12,16,23 In our study, no patient showed any serious side effect.…”

“…16,36 According to the previous studies, single local administration of FGF-2 seems to be well-tolerated and safe. 12,16,23 In our study, no patient showed any serious side effect. However, since 2 patients in the FGF-2 group did not participate in the follow-up evaluations after the intervention, and 2 patients, one from the FGF-2 group and another from control group could not be located till the end of the follow-up period, accurate evaluation of side effects and mortality could not be performed.…”

“…14,15 More importantly, it does not require complicated methods of gene therapy or the exposure to foreign genetic materials with unknown longterm outcomes. 16 The aim of this study was to evaluate the effectiveness and the safety of administering FGF-2 for therapeutic angiogenesis in ischemic myocardium of patients who undergo CABG. Administration of FGF-2 at the onset of ischemia is reported to reduce injury and attenuate heart enzymes.…”

Circulation Research Thematic Synopsis

“…14 However, in spite of plausibility of the approach in provoking new vessel formation and alleviating tissue ischemia, direct delivery of angiogenic factors via gene and cell therapy or protein delivery to the myocardium or peripheral tissues has thus far been unsuccessful clinically. 15,16 Identification of resident and circulating vascular progenitor cells has shifted the emphasis from direct delivery of the angiogenic factors toward harnessing the therapeutic potentials of vascular progenitor cells in angiogenesis. Induced pluripotent stem cells (iPSCs), generated upon expression of a defined set of transcription factors in differentiated cells, 17 as well as bone marrow derived mesenchymal stem cells have been successfully applied in experimental models of angiogenesis.…”

Deficient angiogenesis in redox-dead Cys17Ser PKARIα knock-in mice

“…Inadequate angiogenesis resulting in under-perfusion of tissues mediates many pathologies including peripheral vascular and ischaemic heart disease 1 . Conversely, over-angiogenesis is a common feature of prevalent diseases such as cancer, rheumatoid arthritis and macular degeneration 2 .…”