Therapeutic angiogenesis

While the role of PHD inhibitors in the treatment of anemia is now validated, therapeutic validation is less certain in other HIF-associated pathologies such as wound healing, ulcerative colitis, therapeutic angiogenesis, and treatment of acute ischemic events such as myocardial ischemia and stroke. All of these indications are supported by a compelling array of in vitro and in vivo preclinical studies but their utility in the clinical setting remains to be evaluated and represents exciting possibilities for the future of small-molecule inhibitors of PHD enzymes. 

Hamano K, Nishida M, Hirata K, Mikamo A, Li TS, Harada M, Miura T, Matsuzaki M, Esato K. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease clinical trial and preliminary results. Jpn Circ / 2001 65 845-847. 

Losordo DW, Dimmeler S. Therapeutic angiogenesis and vasculogenesis for ischemic disease part II cell-based therapies. Circulation 2004 109 2692-2697. 

Baumgartner, 1., Therapeutic angiogenesis theoretic problems using vascular endothe-... 

Post, M.J., Laham, R., Sellke, F.W. and Simons, M. (2001) Therapeutic angiogenesis in cardiology using protein formulations. Cardiovasc. Res., 49, 522-531. 

Giacca M (2007) Virus-mediated gene transfer to induce therapeutic angiogenesis where do we stand Int J Nanomedicine 2 527-540... 

Takeshita S, Zheng LR Brogi E, et al, Therapeutic angiogenesis, A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model, J Clin Invest 1994 93(2) 662-670. 

Vale PR, Losordo DW Milliken CE, McDonald MC, Gravelin LM, Curry CM, et al. Randomized, single-blind, placebo-controlled pilot study of catheter-based myocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischemia, Circulation 2001 103 2138-2143. 

The efficacy of gene transfer approaches to therapeutic angiogenesis is now being tested in clinical trials. Controlled phase II trials are providing positive but not definitive results. Gene therapy appears to be safe based on these data. Hard clinical endpoints, such as mortality, myocardial infarction, and the need for revascularization are lacking, as is long-term follow-up. 

Therapeutic angiogenesis is an emerging strategy for treating ischemic diseases by inducing new blood vessel growth in... 

Therapeutic angiogenesis is an experimental area of treatment for cardiac ischemia, which is a common symptom of coronary artery disease. Cardiac ischemia is usually a... 

Udelson JE, Dilsizian V Laham RJ, et al, Therapeutic angiogenesis with recombinant fibroblast growth factor-2 improves stress and rest myocardial perfusion abnormalities in patients with severe symptomatic chronic coronary artery disease. Circulation 2000 102 1605-1610. 

Hamano K, Li TS, Kobayashi T et al. Therapeutic angiogenesis induced by local autologous bone marrow cell implantation, Ann Thorac Surg 2002 73 1210-121 5. 

Tateishi-Yuyama E, Matsubara H, Murohara T, et al, Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators therapeutic angiogenesis for patients with... 

Therapeutic angiogenesis, using growth factors, aims to restore perfusion to chronically ischemic myocardium without intervening on the epicardial coronary arteries, particularly in patients in whom further mechanical revascularization in not possible (Fig. I). Despite initial enthusiasm, therapeutic angiogenesis has not yet provided significant clinical benefit and is still reserved as an experimental treatment for patients who have failed conventional therapies. 

Two approaches have generally been used to achieve therapeutic angiogenesis protein therapy and gene transfer which are briefly discussed next. 

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