Adeno associated viral vector-delivered and hypoxia response element-regulated CD151 expression in ischemic rat heart

Abstract

Aim: The aim of this study was to improve the delivery efficacy and target specificity of the pro-angiogenic gene CD151 to the ischemic heart. Methods: To achieve the inducible expression of adeno-associated viral (AAV)-delivered CD151 gene in only the ischemic myocardium, we generated an AAV construct in which CD151 expression can be controlled by the hypoxia response element (HRE) sequence from the human Enolase gene. The function of this vector was examined in rat H9C2 cardiac myoblasts and in ischemic rat myocardium. The expression of CD151 in the areas of ischemic myocardium was confirmed at the mRNA level by real-time PCR and on the protein level by Western blot, whereas the CD151 expression in the microvessels within the areas of ischemic myocardium was detected by immunohistochemistry. Results: HRE significantly enhances the expression of CD151 under hypoxic conditions or in the ischemic myocardium, and forced CD151 expression increases the number of microvessels in the ischemic myocardium. Conclusion: The AAV-mediated, HRE regulated delivery of the CD151 gene shows higher expression in the ischemic myocardium and more efficiently targets CD151 to the hypoxic regions after myocardial infarction.

Tetraspanins as regulators of the tumour microenvironment: implications for metastasis and therapeutic strategies

“…Angiogenesis has been considered as a prognostic indicator in prostate cancer (Borre et al, 1998;Mehta et al, 2001;Bono et al, 2002) and correlates with the aggressiveness of the disease (Weidner et al, 1993;Ferrer et al, 1998). In animal models of myocardial ischaemia, introduction of CD151 via gene delivery improved capillary densities (Lan et al, 2005;Zuo et al, 2009a;Wei et al, 2011). Studies using CD151-null mice found that these mice were viable and no phenotypic change was reported.…”

Acceleration of gene transfection efficiency in neuroblastoma cells through polyethyleneimine/poly(methyl methacrylate) core-shell magnetic nanoparticles

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