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Invited Review

Genetic targeting for cardiovascular therapeutics: are we near the summit or just beginning the climb?

¹ Department of Physiology and Functional Genomics, College of Medicine, University of Florida Brain Institute, Gainesville, Florida 32610
² Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
³ Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115
⁴ Departments of Vascular Medicine
⁵ Cardiology, St. Elizabeth’s Medical Center, Tuft’s University School of Medicine, Boston, Massachusetts 02135
⁶ Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425
⁷ Department of Pharmacodynamics, College of Pharmacy, Gainesville, Florida 32610
⁸ Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294

This article is based on an Experimental Biology symposium held in April 2001 and presents the current status of gene therapy for cardiovascular diseases in experimental studies and clinical trials. Evidence for the use of gene therapy to limit neointimal hyperplasia and confer myocardial protection was presented, and it was found that augmenting local nitric oxide (NO) production using gene transfer (GT) of NO synthase or interruption of cell cycle progression through a genetic transfer of cell cycle regulatory genes limited vascular smooth muscle hyperplasia in animal models and infra-inguinal bypass patients. The results of application of vascular endothelial growth factor (VEGF) GT strategies for therapeutic angiogenesis in critical limb and myocardial ischemia in pilot clinical trials was reviewed. In addition, experimental evidence was presented that genetic manipulation of peptide systems (i.e., the renin-angiotensin II system and the kallikrein-kinin system) was effective in the treatment of systemic cardiovascular diseases such as hypertension, heart failure, and renal failure. Although, as of yet, there are no well controlled human trials proving the clinical benefits of gene therapy for cardiovascular diseases, the data presented here in animal models and in human subjects show that genetic targeting is a promising and encouraging modality, not only for the treatment and long-term control of cardiovascular diseases, but for their prevention as well.

gene therapy; angiogenesis; vascular endothelial growth factor; myocardial and limb ischemia; neointimal hyperplasia

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