CD151 Gene Delivery Activates PI3K/Akt Pathway and Promotes Neovascularization after Myocardial Infarction in Rats

Zheng, Zhenzhong; Liu, Zhengxiang

doi:10.2119/2006-00037.zheng

Cited by 36 publications

(19 citation statements)

References 28 publications

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“…Exogenous nerve growth factor supports angiogenesis and myocyte survival in infarcted murine hearts via the AKT/FOXO pathway (78, 475). CD151 induces endothelial cell proliferation, migration, and neovascularization in infarcted hearts via PI3K/AKT activation (695, 696), while periostin signals through FAK and AKT to mediate recruitment of activated cardiac fibroblasts to sites of cardiac injury following acute myocardial infarction (581). Intracardiac injection of SDF-1a into infarcted mouse heart improves cardiomyocyte survival and increases neoangiogenesis, potentially via activation of AKT (572).…”

Section: Akt In the Myocardial Contextmentioning

confidence: 99%

Myocardial AKT: The Omnipresent Nexus

Sussman

Völkers

Fischer

et al. 2011

Physiological Reviews

198

173

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One of the greatest examples of integrated signal transduction is revealed by examination of effects mediated by AKT kinase in myocardial biology. Positioned at the intersection of multiple afferent and efferent signals, AKT exemplifies a molecular sensing node that coordinates dynamic responses of the cell in literally every aspect of biological responses. The balanced and nuanced nature of homeostatic signaling is particularly essential within the myocardial context, where regulation of survival, energy production, contractility, and response to pathological stress all flow through the nexus of AKT activation or repression. Equally important, the loss of regulated AKT activity is primarily the cause or consequence of pathological conditions leading to remodeling of the heart and eventual decompensation. This review presents an overview compendium of the complex world of myocardial AKT biology gleaned from more than a decade of research. Summarization of the widespread influence that AKT exerts upon myocardial responses leaves no doubt that the participation of AKT in molecular signaling will need to be reckoned with as a seemingly omnipresent regulator of myocardial molecular biological responses.

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Section: Akt In the Myocardial Contextmentioning

confidence: 99%

Myocardial AKT: The Omnipresent Nexus

Sussman

Völkers

Fischer

et al. 2011

Physiological Reviews

198

173

View full text Add to dashboard Cite

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“…The a6b4 and a3b1 integrins regulate the migration of epithelial cells through a direct interaction of these integrins with the C-terminal domain of netrin-1, and the modulatory activity of CD151 is dependent on its association with the a3b1 and a6b4 integrins [23,24]. CD151 was shown to promote neovascularization and angiogenesis in a rat model of hindlimb ischemia and to improve ventricular function after myocardial infarction in rats [25,26].…”

Section: Introductionmentioning

confidence: 99%

CD151 mediates netrin‐1‐induced angiogenesis through the Src‐FAK‐Paxillin pathway

Yang

Zhong

et al. 2016

J Cellular Molecular Medi

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Crosstalk between the nervous and vascular systems is important during development and in response to injury, and the laminin‐like axonal guidance protein netrin‐1 has been studied for its involvement in angiogenesis and vascular remodelling. In this study, we examined the role of netrin‐1 in angiogenesis and explored the underlying mechanisms. The effect of netrin‐1 on brain tissues and endothelial cells was examined by immunohistochemistry and western blotting in a middle cerebral artery occlusion model and in human umbilical vein endothelial cells. Cell proliferation and cell cycle progression were assessed by the MTT assay and flow cytometry, and the Transwell and tube formation assays were used to examine endothelial cell motility and function. Netrin‐1 up‐regulated CD151 and VEGF concomitant with the activation of focal adhesion kinase (FAK), Src and Paxillin in vitro and in vivo and the induction of cell proliferation, migration and tube formation in vitro. Silencing of CD151 abolished the effects of netrin‐1 on promoting cell migration and tube formation mediated by the activation of FAK/Src signalling. Netrin‐1 promoted angiogenesis in vitro and in vivo by activating the FAK/Src/Paxillin signalling pathway through a mechanism dependent on the expression of the CD151 tetraspanin, suggesting the existence of a netrin‐1/FAK/Src/CD151 signalling axis involved in the modulation of angiogenesis.

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“…Conversely, overexpression of CD151 in human umbilical vein ECs enhances cell proliferation, migration, and capillary tube formation on Matrigel [22] . We have reported that CD151 gene delivery increased the number of microvessels in a rat myocardial ischemia model and a rat ischemic hindlimb model [1,2] . Further study underlined that CD151 gene delivery promoted angiogenesis in a pig myocardial ischemia model and demonstrated that CD151-induced neovascularization effectively enhanced the myocardial perfusion and markedly ameliorated the regional myocardial dysfunction based on 13 N-NH 3 PET imaging and echocardiography [3,4] .…”

Section: Discussionmentioning

confidence: 97%

“…Our previous studies have demonstrated that direct injection of an AAV vector carrying CD151 gene to rat ischemic hind limb induced neovasculature formation, and CD151 gene delivery increased the number of microvessels in a rat ischemic myocardium model [1,2] . Further study indicated that CD151 gene delivery induced angiogenesis by increasing the capillary and arteriole density in a swine myocardial infarction model [3,4] .…”

mentioning

confidence: 99%

Adeno-associated viral vector mediated and cardiac-specific delivery of CD151 gene in ischemic rat hearts

Quan

Liu

Fei

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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Our previous studies demonstrated that CD151 gene promoted neovascularization in ischemic heart model. To improve the delivery efficacy and target specificity of CD151 gene to ischemic heart, we generated an adeno-associated virus (AAV) vector in which CD151 expression was controlled by the myosin light chain (MLC-2v) promoter to achieve the cardiac-specific expression of CD151 gene in ischemic myocardium and to limit unwanted CD151 expression in extracardiac organs. The function of this vector was examined in rat ischemic myocardium model. The protein expression of CD151 in the ischemic myocardium areas, liver and kidney was confirmed by using Western blot, while the microvessels within ischemic myocardium areas were detected by using immunohistochemistry. The results showed that MLC-2v significantly enhanced the expression of CD151 in ischemic myocardium, but attenuated its expression in other organs. The forced CD151 expression could increase the number of microvessels in the ischemic myocardium. This study demonstrates the AAV-mediated and MLC-2v regulated CD151 gene is highly expressed in the ischemic myocardium and cardiac-specific delivery that is more efficiently targets CD151 to the ischemia myocardium after myocardial infarction.

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CD151 Gene Delivery Activates PI3K/Akt Pathway and Promotes Neovascularization after Myocardial Infarction in Rats

Cited by 36 publications

References 28 publications

Myocardial AKT: The Omnipresent Nexus

Myocardial AKT: The Omnipresent Nexus

CD151 mediates netrin‐1‐induced angiogenesis through the Src‐FAK‐Paxillin pathway

Adeno-associated viral vector mediated and cardiac-specific delivery of CD151 gene in ischemic rat hearts

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