Abstract
Aim:
To appraise the efficacy of CD151-induced myocardial therapeutic angiogenesis in a pig myocardial infarction model.
Methods:
CD151 and anti-CD151 were constructed into the recombinant adeno-associated virus (rAAV) vector. All 26 pigs were subjected to coronary artery ligation or no surgery. Eight weeks after coronary artery ligation, the expression of CD151 was measured by Western blot and immunostaining. Capillary density was evaluated using immunostaining for von Willebrand factor (vWF). 13N-labeled NH3 positron emission computed tomography ([13N]NH3 PET) was measured to assess regional myocardial perfusion and the defect area.
Results:
CD151 gene delivery could increase the expression of CD151 at protein level. Over-expression of CD151 increased the density of total capillaries in the ischemic myocardium, significantly improved the blood perfusion and reduced the defect area percentage.
Conclusion:
This study demonstrated that the rAAV-mediated CD151 gene delivery promoted efficient neovascularization and increased the blood perfusion after myocardial infarction in pigs.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Lee LY, Patell SR, Hackett NR, Mack CA, Polce DR, El-Sawy T, et al. Focal angiogen therapy using intramyocardial delivery of an adenovirus vector coding for vascular endothelial growth factor 121. Ann Thorac Surg 2000; 69: 14–23.
Taniyama Y, Morishita R, Aoki M, Nakagami H, Yamamoto K, Yamazaki K, et al. Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease. Gene Ther 2001; 8: 181–9.
Fitter S, Tetaz TJ, Berndt MC, Ashman LK. Molecular cloning of cDNA encoding a novel platelet-endothelial cell tetra-span antigen, PETA-3. Blood 1995; 86: 1348–55.
Hasegawa H, Utsunomiya Y, Kishimoto K, Yanagisawa K, Fujita S. SFA-1, a novel cellular gene induced by human T-cell leukemia virus type 1, is a member of the transmembrane 4 superfamily. J Virol 1996; 70: 3258–63.
Sincock PM, Mayrhofer G, Ashman LK. Localization of the transmembrane 4 superfamily (TM4SF) member PETA-3 (CD151) in normal human tissues: comparison with CD9, CD63, and alpha5beta1 integrin. J Histochem Cytochem 1997; 45: 515–25.
Sincock PM, Fitter S, Parton RG, Berndt MC, Gamble JR, Ashman LK. PETA-3/CD151, a member of the transmembrane 4 superfamily, is localised to the plasma membrane and endocytic system of endothelial cells, associates with multiple integrins and modulates cell function. J Cell Sci 1999; 112: 833–44.
Yauch RL, Berditchevski F, Harler MB, Reichner J, Hemler ME. Highly stoichiometric, stable, and specific association of integrin alpha3beta1 with CD151 provides a major link to phosphatidylinositol 4-kinase, and may regulate cell migration. Mol Biol Cell 1998; 9: 2751–65.
Zhang XA, Kazarov AR, Kazarov AR, Yang X, Bontrager AL, Stipp CS, et al. Function of the tetraspanin CD151-alpha6beta1 integrin complex during cellular morphogenesis. Mol Biol Cell 2002; 13: 1–11.
Hemler ME. Integrin-associated proteins. Curr Opin Cell Biol 1998; 10: 578–85.
Yáñez-Mó M, Alfranca A, Cabañas C, Marazuela M, Tejedor R, Ursa MA, et al. Regulation of endothelial cell motility by complexes of tetraspan molecules CD81/TAPA-1 and CD151/PETA-3 with alpha3 beta1 integrin localized at endothelial lateral junctions. J Cell Biol 1998; 141: 791–804.
Zheng ZZ, Liu ZX. Activation of the phosphatidylinositol 3-kinase/protein kinase Akt pathway mediates CD151-induced endothelial cell proliferation and cell migration. Int J Biochem Cell Biol 2007; 39: 340–8.
Zheng ZZ, Liu ZX. CD151 gene delivery increases eNOS activity and induces ECV304 migration, proliferation and tube formation. Acta Pharmacol Sin 2007; 28: 66–72.
Zheng ZZ, Liu ZX. CD151 gene delivery activates PI3K/Akt pathway and promotes neovascularization after myocardial infarction in rats. Mol Med 2006; 12: 214–20.
Lan RF, Liu ZX, Liu XC, Song YE, Wang DW. CD151 promotes neovascularization and improves blood perfusion in a rat hind-limb ischemia model. J Endovasc Ther 2005; 12: 469–78.
Markkanen JE, Rissanen TT, Kivelä A, Ylä-Herttuala S. Growth factor-induced therapeutic angiogenesis and arteriogenesis in the heart-gene therapy. Cardiovasc Res 2005; 65: 656–64.
Lan R, Liu Z, Song YE, Zhang X. Effects of rAAV-CD151 and rAAV-antiCD151 on the migration of human tongue squamous carcinoma cell line Tca8113. J Huazhong Univ Sci Technol Med Sci 2004; 24: 556–9.
Xiao X, Li J, Samulski RJ. Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J Virol 1998; 72: 2224–32.
Weidner N, Folkman, Pozza F, Bevilacqua P, Allred EN, Moore DH, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 1992; 84: 1875–87.
Buschmann I, Schaper W. Arteriogenesis versus angiogenesis: two mechanism of vessel growth. News Physiol Sci 1999; 14: 121–5.
Hong IK, Jin YJ, Byun HJ, Jeoung DI, Kim YM, Lee H. Homophilic interactions of Tetraspanin CD151 up-regulate motility and matrix metalloproteinase-9 expression of human melanoma cells through adhesion-dependent c-Jun activation signaling pathways. J Biol Chem 2006; 281: 24279–92.
Sugiura T, Berditchevski F. Function of alpha3beta1-tetraspanin protein complexes in tumor cell invasion. Evidence for the role of the complexes in production of matrix metalloproteinase 2 (MMP-2). J Cell Biol 1999; 146: 1375–89.
Shiomi T, Inoki I, Kataoka F, Ohtsuka T, Hashimoto G, Nemori R, et al. Pericellular activation of proMMP-7 (promatrilysin-1) through interaction with CD151. Lab Invest 2005; 85: 1489–506.
Klosek SK, Nakashiro K, Hara S, Shintani S, Hasegawa H, Hamakawa H. CD151 forms a functional complex with c-Met in human salivary gland cancer cells. Biochem Biophys Res Commun 2005; 336: 408–16.
Aoki M, Morishita R, Taniyama Y, Kida I, Moriguchi A, Matsumoto K, et al. Angiogenesis induced by hepatocyte growth factor in non-infarcted myocardium and infarcted myocardium: up-regulation of essential transcription factor for angiogenesis. Gene Ther 2000; 7: 417–27.
Rutanen J, Rissanen TT, Markkanen JE, Gruchala M, Silvennoinen P, Kivela A, et al. Adenoviral catheter-mediated intramyocardial gene transfer using the mature form of vascular endothelial growth factor-D induces transmural angiogenesis in porcine heart. Circulation 2004; 109: 1029–35.
Gruchala M, Bhardwaj S, Pajusola K, Roy H, Rissanen TT, Kokina I, et al. Gene transfer into rabbit arteries with adeno-associated virus and adenovirus vectors. J Gene Med 2004; 6: 545–54.
Wang Z, Ma HI, Li J, Sun L, Zhang J, Xiao X. Rapid and highly efficient transduction by double-standed adeno-associated virus vectors in vitro and in vivo. Gene Ther 2003; 10: 2105–11.
Acknowledgements
Project was supported by grants from the National Natural Science Foundation of China (No 30570728; No 30670856).
We thank Dr Xin ZHANG for providing PzeoSV-CD151 plasmid and Dr Xiao XIAO (University of Pittsburgh, PA, USA) for providing us with dsAAV-GFP, pXX2, phelper.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zuo, Hj., Liu, Zx., Liu, Xc. et al. Assessment of myocardial blood perfusion improved by CD151 in a pig myocardial infarction model. Acta Pharmacol Sin 30, 70–77 (2009). https://doi.org/10.1038/aps.2008.10
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/aps.2008.10
Keywords
This article is cited by
-
Comparative analysis of peripheral blood reveals transcriptomic adaptations to extreme environments on the Qinghai-Tibetan Plateau in the gray wolf (Canis lupus chanco)
Organisms Diversity & Evolution (2019)
-
Tetraspanin proteins promote multiple cancer stages
Nature Reviews Cancer (2014)
-
Adeno associated viral vector-delivered and hypoxia response element-regulated CD151 expression in ischemic rat heart
Acta Pharmacologica Sinica (2011)
-
Adeno-associated viral vector mediated and cardiac-specific delivery of CD151 gene in ischemic rat hearts
Journal of Huazhong University of Science and Technology [Medical Sciences] (2011)
-
Activation of the ERK signaling pathway is involved in CD151-induced angiogenic effects on the formation of CD151-integrin complexes
Acta Pharmacologica Sinica (2010)


