Genetic targeting for cardiovascular therapeutics: are we near the summit or just beginning the climb?
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.
Francis
S C
SC
Department of Physiology and Functional Genomics, College of Medicine, University of Florida Brain Institute, Gainesville, Florida 32610, USA.
Raizada
M K
MK
Mangi
A A
AA
Melo
L G
LG
Dzau
V J
VJ
Vale
P R
PR
Isner
J M
JM
Losordo
D W
DW
Chao
J
J
Katovich
M J
MJ
Berecek
K H
KH
D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics / Q000628:therapy*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003226:Congresses as Topic; D016228:Endothelial Growth Factors / Q000235:genetics / Q000627:therapeutic use; D018390:Gene Targeting / Q000379:methods* / Q000639:trends; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods* / Q000639:trends; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006801:Humans; D008222:Lymphokines / Q000235:genetics / Q000627:therapeutic use; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018797:Cell Cycle Proteins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019001:Nitric Oxide Synthase