Synergistically Combined Gene Delivery for Enhanced VEGF Secretion and Antiapoptosis

Overview

Journal Mol Pharm

Publisher American Chemical Society

Specialty Pharmacology

Date 2013 Sep 7

PMID 24007285

Citations 10

Authors

Young-Wook Won

Minhyung Lee

Hyun Ah Kim

Kihoon Nam

David A Bull

Sung Wan Kim

Affiliations

Soon will be listed here.

Abstract

With current pharmacological treatments, preventing the remodeling of the left ventricle and the progression to heart failure is a difficult task. Gene therapy is considered to provide a direct treatment to the long-term complications of ischemic heart diseases. Although current gene therapies that use single molecular targets seem potentially possible, they have not achieved success in the treatment of ischemic diseases. With an efficient polymeric gene carrier, PAM-ABP, we designed a synergistically combined gene-delivery strategy to enhance vascular endothelial growth factor (VEGF) secretion and to prolong its antiapoptotic effects. A hypoxia-inducible plasmid expressing both hypoxia-inducible heme oxygenase-1 (HO-1) and the Src homology domain-2 containing tyrosine phosphatase-1 microRNA (miSHP-1) as well as a hypoxia-responsive VEGF plasmid were combined in this study. The positive feedback circuit between HO-1 and VEGF and the negative regulatory role of SHP-1 in angiogenesis enhance VEGF secretion synergistically. The synergy in VEGF secretion as a consequence of the gene combination and prolonged HO-1 activity was confirmed in hypoxic cardiomyocytes and cardiomyocyte apoptosis under hypoxia and was decreased synergistically. These results suggest that the synergistic combination of VEGF, HO-1, and miSHP-1 may be promising for the clinical treatment of ischemic diseases.

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References

Nam H, Kim J, Kim S, Yockman J, Kim S, Bull D . Cell penetrating peptide conjugated bioreducible polymer for siRNA delivery. Biomaterials. 2011; 32(22):5213-22. PMC: 3128881. DOI: 10.1016/j.biomaterials.2011.03.058. View

Lee Y, Jeon K, Lee J, Kim S, Kim V . MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002; 21(17):4663-70. PMC: 126204. DOI: 10.1093/emboj/cdf476. View

Stocker R, Perrella M . Heme oxygenase-1: a novel drug target for atherosclerotic diseases?. Circulation. 2006; 114(20):2178-89. DOI: 10.1161/CIRCULATIONAHA.105.598698. View

Chong Z, Maiese K . The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury. Histol Histopathol. 2007; 22(11):1251-67. PMC: 2515712. DOI: 10.14670/HH-22.1251. View

Wo Y, McCormack A, Shabanowitz J, Hunt D, Davis J, Mitchell G . Sequencing, cloning, and expression of human red cell-type acid phosphatase, a cytoplasmic phosphotyrosyl protein phosphatase. J Biol Chem. 1992; 267(15):10856-65. View

Matsui T, Tao J, Del Monte F, Lee K, Li L, Picard M . Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation. 2001; 104(3):330-5. DOI: 10.1161/01.cir.104.3.330. View

Bussolati B, Mason J . Dual role of VEGF-induced heme-oxygenase-1 in angiogenesis. Antioxid Redox Signal. 2006; 8(7-8):1153-63. DOI: 10.1089/ars.2006.8.1153. View

May D, Gilon D, Djonov V, Itin A, Lazarus A, Gordon O . Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation. Proc Natl Acad Sci U S A. 2007; 105(1):282-7. PMC: 2224202. DOI: 10.1073/pnas.0707778105. View

Won Y, Lee M, Kim H, Bull D, Kim S . Post-translational regulated and hypoxia-responsible VEGF plasmid for efficient secretion. J Control Release. 2012; 160(3):525-31. PMC: 3372625. DOI: 10.1016/j.jconrel.2012.03.010. View

10.

Lin H, Chen Y, Chang P, Lee Y, Yet S, Chau L . Heme oxygenase-1 promotes neovascularization in ischemic heart by coinduction of VEGF and SDF-1. J Mol Cell Cardiol. 2008; 45(1):44-55. DOI: 10.1016/j.yjmcc.2008.04.011. View

11.

Nam H, Nam K, Lee M, Kim S, Bull D . Dendrimer type bio-reducible polymer for efficient gene delivery. J Control Release. 2012; 160(3):592-600. DOI: 10.1016/j.jconrel.2012.04.025. View

12.

Yet S, Tian R, Layne M, Wang Z, Maemura K, Solovyeva M . Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice. Circ Res. 2001; 89(2):168-73. DOI: 10.1161/hh1401.093314. View

13.

Deramaudt B, Braunstein S, Remy P, Abraham N . Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis. J Cell Biochem. 1998; 68(1):121-7. DOI: 10.1002/(sici)1097-4644(19980101)68:1<121::aid-jcb12>3.0.co;2-k. View

14.

Kim T, Ou M, Lee M, Kim S . Arginine-grafted bioreducible poly(disulfide amine) for gene delivery systems. Biomaterials. 2008; 30(4):658-64. PMC: 2642962. DOI: 10.1016/j.biomaterials.2008.10.009. View

15.

Hirai K, Sasahira T, Ohmori H, Fujii K, Kuniyasu H . Inhibition of heme oxygenase-1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL mice. Int J Cancer. 2006; 120(3):500-5. DOI: 10.1002/ijc.22287. View

16.

Vulapalli S, Chen Z, Chua B, Wang T, Liang C . Cardioselective overexpression of HO-1 prevents I/R-induced cardiac dysfunction and apoptosis. Am J Physiol Heart Circ Physiol. 2002; 283(2):H688-94. DOI: 10.1152/ajpheart.00133.2002. View

17.

Dai Y, Xu M, Wang Y, Pasha Z, Li T, Ashraf M . HIF-1alpha induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia. J Mol Cell Cardiol. 2007; 42(6):1036-44. PMC: 1995444. DOI: 10.1016/j.yjmcc.2007.04.001. View

18.

Dulak J, Zagorska A, Wegiel B, Loboda A, Jozkowicz A . New strategies for cardiovascular gene therapy: regulatable pre-emptive expression of pro-angiogenic and antioxidant genes. Cell Biochem Biophys. 2006; 44(1):31-42. PMC: 1391923. DOI: 10.1385/CBB:44:1:031. View

19.

Daigle I, Yousefi S, Colonna M, Green D, Simon H . Death receptors bind SHP-1 and block cytokine-induced anti-apoptotic signaling in neutrophils. Nat Med. 2002; 8(1):61-7. DOI: 10.1038/nm0102-61. View

20.

Klingmuller U, Lorenz U, Cantley L, Neel B, Lodish H . Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals. Cell. 1995; 80(5):729-38. DOI: 10.1016/0092-8674(95)90351-8. View