Gene therapy progress and prospects: therapeutic angiogenesis for ischemic cardiovascular disease.

During the past decade, both in vitro and in vivo studies have provided new insights into the cellular and molecular mechanisms that govern angiogenesis and arteriogenesis. However, therapeutic angiogenesis clinical trials using recombinant protein or gene therapy formulations of single angiogenic growth factors have yielded at best only modest success to date. Among the second generation of angiogenic agents are therapeutic transgenes that enhance expression of two or more proangiogenic cytokines. These include synthetic constructs that mimic that activity of endogenous transcriptional regulators and other upstream, regulatory factors that have the potential to induce formation of morphologically and physiologically functional vessels. These agents are now beginning to be evaluated in clinical trials for patients with advanced ischemic cardiac and peripheral vascular disease.