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(Circulation Research. 2006;98:1115.)
© 2006 American Heart Association, Inc.

Editorials

Therapeutic Angiogenesis

Another Passing Phase?

Gregg L. Semenza

From the Vascular Biology Program, Institute for Cell Engineering; Departments of Pediatrics, Medicine, Oncology, and Radiation Oncology; and McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore.

Correspondence to Gregg L. Semenza, MD, PhD, Broadway Research Building, Suite 671, The Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205. E-mail gsemenza@jhmi.edu

See related article, pages 1194–1202

Key Words: bone marrow • endothelial progenitor • ischemia

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Efforts to stimulate tissue vascularization in patients with ischemia resulting from coronary or peripheral arterial disease (therapeutic angiogenesis^1,2) have passed through several scientific phases over the last dozen years, based on our increased understanding of the molecular mechanisms underlying vascular homeostasis (Table). In the first phase, a single angiogenic growth factor, or its cognate DNA sequence, was injected into ischemic tissue.^2,3 In the case of angiogenic growth factor gene therapy, the goal was to augment production of the angiogenic factor by the patient’s own cardiac or skeletal muscle cells. The angiogenic factor, as exemplified by vascular endothelial growth factor (VEGF), was believed to act by binding to receptors that were expressed on the surface of endothelial cells, activating the cells to migrate, proliferate, and form new or large vessels, thus allowing increased perfusion of tissue surrounding the injection site. The administration of these factors worked well in accelerating the recovery of perfusion in healthy young laboratory animals subjected to an acute interruption of coronary or femoral arterial blood flow. Encouraging results were also obtained in early clinical trials that lacked control populations. However, the double-blind placebo-controlled VIVA study of VEGF in patients with myocardial ischemia showed no significant objective benefit of therapy but instead revealed a placebo effect that was remarkable in its magnitude.⁴

View this table: [in this window] [in a new window]   Table 1. Molecular Mechanisms of Angiogenesis: A Brief Scientific History

The second phase of therapeutic angiogenesis began with the identification of circulating bone marrow–derived cells, which expressed markers of both hematopoietic progenitor cells (CD34, c-kit) . . . [Full Text of this Article]

Related Article:

Critical Roles of Muscle-Secreted Angiogenic Factors in Therapeutic Neovascularization

Kaoru Tateno, Tohru Minamino, Haruhiro Toko, Hiroshi Akazawa, Naomi Shimizu, Shinichi Takeda, Takeshige Kunieda, Hideyuki Miyauchi, Tomomi Oyama, Katsuhisa Matsuura, Jun-ichiro Nishi, Yoshio Kobayashi, Toshio Nagai, Yoichi Kuwabara, Yoichiro Iwakura, Fumio Nomura, Yasushi Saito, and Issei Komuro
Circ. Res. 2006 98: 1194-1202. [Abstract] [Full Text] [PDF]

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