This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Melo, L. G. Articles by Dzau, V. J. Search for Related Content PubMed PubMed Citation Articles by Melo, L. G. Articles by Dzau, V. J. Related Collections Other myocardial biology Ischemic biology - basic studies Physiological and pathological control of gene expression Acute myocardial infarction Chronic ischemic heart disease Gene therapy Oxidant stress

(Circulation. 2004;109:2386-2393.)
© 2004 American Heart Association, Inc.

Review: Current Perspective

Molecular and Cell-Based Therapies for Protection, Rescue, and Repair of Ischemic Myocardium

Reasons for Cautious Optimism

Luis G. Melo, PhD; Alok S. Pachori, PhD; Deling Kong, PhD; Massimiliano Gnecchi, MD; Kai Wang, MD; Richard E. Pratt, PhD; Victor J. Dzau, MD

From the Department of Physiology (L.G.M., K.W.), Queen’s University, Kingston, Ontario, Canada, and Department of Medicine (L.G.M., A.S.P., D.K., M.G., R.E.P., V.J.D.), Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Luis G. Melo, PhD, Department of Physiology, Queen’s University, 20 Stuart St, Kingston, Ontario K7L 3N6, Canada. E-mail melol@post.queensu.ca

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

	Introduction

 
Despite the significant therapeutic advances of the past 25 years, coronary ischemic artery disease (CAD) remains the predominant cause of premature death.^1,2 The prevalence of the disease imposes enormous financial strain on the healthcare system,^2,3 calling for new approaches for treatment of CAD. The availability of cardiotropic vectors capable of long-term and stable protein expression⁴ and the recent isolation of progenitor cells with regenerative and angiogenic potential^5,6 may provide opportunities for the design of novel therapies for protection and rescue of the myocardium from ischemia and failure. Cardioprotective gene therapy strategies have been effective in animal models of myocardial ischemia and reperfusion injury,^7,8 and gene transfer of proangiogenic cytokines has been used as a strategy for rescuing ischemic myocardium.⁹ Transplantation of autologous progenitor cells is emerging as a potential option for the revascularization and repair of ischemic and infarcted myocardium.⁶ Notwithstanding these promising findings, there is pressing need for the development of safer and more effective vectors and the optimization and standardization of gene- and cell-based therapies.

In this article, we discuss the current preclinical and clinical advances in gene- and cell-based therapies for protection, rescue, and repair of the ischemic myocardium, with emphasis on strategies for protection of the myocardium from ischemia and reperfusion injury and for neovascularization and regeneration of ischemic and infarcted myocardium.

	Gene Therapy for Protection of Myocardium at Risk

 
The development of gene therapies for acute myocardial infarction (MI) is not possible with the current vectors because the time required for transcription and translation of therapeutic genes exceeds the time window for successful . . . [Full Text of this Article]

This article has been cited by other articles:

				M. A. Kuliszewski, H. Fujii, C. Liao, A. H. Smith, A. Xie, J. R. Lindner, and H. Leong-Poi Molecular imaging of endothelial progenitor cell engraftment using contrast-enhanced ultrasound and targeted microbubbles Cardiovasc Res, September 1, 2009; 83(4): 653 - 662. [Abstract] [Full Text] [PDF]

				M. Gnecchi, Z. Zhang, A. Ni, and V. J. Dzau Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy Circ. Res., November 21, 2008; 103(11): 1204 - 1219. [Abstract] [Full Text] [PDF]

				R. Senior To revascularize or not to revascularize: a dilemma in heart failure. Can. Med. Assoc. J., August 15, 2006; 175(4): 372 - 372. [Full Text] [PDF]

				M. Gnecchi, H. He, N. Noiseux, O. D. Liang, L. Zhang, F. Morello, H. Mu, L. G. Melo, R. E. Pratt, J. S. Ingwall, et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement FASEB J, April 1, 2006; 20(6): 661 - 669. [Abstract] [Full Text] [PDF]

				V. J. Dzau, M. Gnecchi, and A. S. Pachori Enhancing Stem Cell Therapy Through Genetic Modification J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1351 - 1353. [Full Text] [PDF]

				M. L. Springer, R. E. Sievers, M. N. Viswanathan, M. S. Yee, E. Foster, W. Grossman, and Y. Yeghiazarians Closed-chest cell injections into mouse myocardium guided by high-resolution echocardiography Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1307 - H1314. [Abstract] [Full Text] [PDF]

				P. Chareonthaitawee, B. J. Gersh, P. A. Araoz, and R. J. Gibbons Revascularization in Severe Left Ventricular Dysfunction: The Role of Viability Testing J. Am. Coll. Cardiol., August 16, 2005; 46(4): 567 - 574. [Abstract] [Full Text] [PDF]