The Induction of Yes-Associated Protein Expression After Arterial Injury Is Crucial for Smooth Muscle Phenotypic Modulation and Neointima Formation

Wang, Xiaobo; Hu, Guoqing; Gao, Xinliang; Wang, Yong; Zhang, Wei; Harmon, Erin Y.; Zhi, Xu; Xu, Zhengping; Lennartz, Michelle R.; Barroso, Margarida; Trebak, Mohamed; Chen, Ceshi; Zhou, Jiliang

doi:10.1161/atvbaha.112.254730

Cited by 105 publications

(152 citation statements)

References 32 publications

(46 reference statements)

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“…Besides TxA2, isoprostanes may also act through the TP receptor on the surface of smooth muscle cells and initiate the migration from media to intima via YAP/TAZ activation. Previous studies have reported that YAP is activated in VSMCs of the neointima (39). We propose that thromboxane acts through TP to induce YAP/TAZ activation to promote normal physiological wound healing in response to vascular injury.…”

Section: Discussionmentioning

confidence: 71%

“…Interestingly, emerging evidence shows that YAP is induced after arterial injury and that its activation promotes smooth muscle phenotypic switching and neointima formation (39,40). This led us to investigate the function of YAP/TAZ in TxA2-and TP receptor-induced cellular signaling and VSMC migration and proliferation.…”

Section: Tp-specific Agonists [1s-[1␣2␣(z)3␤(1e3s*)4 ␣]]-7-[3-[3-mentioning

confidence: 99%

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Thromboxane A2 Activates YAP/TAZ Protein to Induce Vascular Smooth Muscle Cell Proliferation and Migration

Liu

Zhou

et al. 2016

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 71%

Section: Tp-specific Agonists [1s-[1␣2␣(z)3␤(1e3s*)4 ␣]]-7-[3-[3-mentioning

confidence: 99%

Thromboxane A2 Activates YAP/TAZ Protein to Induce Vascular Smooth Muscle Cell Proliferation and Migration

Liu

Zhou

et al. 2016

Journal of Biological Chemistry

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“…In the vascular system, smooth muscle-specific deletions of YAP result in profound cardiac defects and vascular abnormalities (28). The inductions of YAP expression and activation following arterial injury enhance neointima formation and the subsequent stenosis as a result of the unrestrained smooth muscle cell proliferation (15). We demonstrate that perturbations of YAP/TAZ in ECs resulted in significant changes in EC growth, indicating that YAP/TAZ are essential for proliferation and cell cycle progression of ECs.…”

Section: Discussionmentioning

confidence: 75%

“…Recent studies have reported that YAP/TAZ serve as major mechanotransducers responding to extracellular biophysical cues, such as cell geometry and matrix stiffness, in modulating stem cell fate (14). YAP has been shown to mediate vascular remodeling in the progression of carotid stenosis (15). Two of the YAP/TAZ transcriptional targets, cysteine-rich angiogenic inducer 61 (CYR61) and connective tissue growth factor (CTGF), are highly expressed in atherosclerotic or injured, but not in normal, human arteries (16,17).…”

mentioning

confidence: 99%

Flow-dependent YAP/TAZ activities regulate endothelial phenotypes and atherosclerosis

Wang

Yeh

Nguyen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

365

352

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The focal nature of atherosclerotic lesions suggests an important role of local hemodynamic environment. Recent studies have demonstrated significant roles of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in mediating mechanotransduction and vascular homeostasis. The objective of this study is to investigate the functional role of YAP/TAZ in the flow regulation of atheroprone endothelial phenotypes and the consequential development of atherosclerotic lesions. We found that exposure of cultured endothelial cells (ECs) to the atheroprone disturbed flow resulted in YAP/TAZ activation and translocation into EC nucleus to up-regulate the target genes, including cysteine-rich angiogenic inducer 61 (CYR61), connective tissue growth factor (CTGF), and ankyrin repeat domain 1 (ANKRD1). In contrast, the atheroprotective laminar flow suppressed YAP/TAZ activities. En face analysis of mouse arteries demonstrated an increased nuclear localization of YAP/TAZ and elevated levels of the target genes in the endothelium in atheroprone areas compared with athero-protective areas. YAP/TAZ knockdown significantly attenuated the disturbed flow induction of EC proliferative and proinflammatory phenotypes, whereas overexpression of constitutively active YAP was sufficient to promote EC proliferation and inflammation. In addition, treatment with statin, an antiatherosclerotic drug, inhibited YAP/TAZ activities to diminish the disturbed flow-induced proliferation and inflammation. In vivo blockade of YAP/TAZ translation by morpholino oligos significantly reduced endothelial inflammation and the size of atherosclerotic lesions. Our results demonstrate a critical role of the activation of YAP/TAZ by disturbed flow in promoting atheroprone phenotypes and atherosclerotic lesion development. Therefore, inhibition of YAP/TAZ activation is a promising athero-protective therapeutic strategy.atherogenesis | disturbed flow | endothelial cells | mechanotransduction

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“…For example, Yap expression is significantly increased in smooth muscle cells following carotid artery injury, where it promotes smooth muscle proliferation and migration (Wang et al, 2012). Although Yap and Taz are thought to mediate largely redundant functions in many tissues, deletion of Yap in developing smooth muscle is sufficient to disrupt smooth muscle formation, producing thin arterial walls and enlarged vessel lumens in the left carotid and thoracic arteries (Wang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Hippo signaling is required for Notch-dependent smooth muscle differentiation of neural crest

et al. 2015

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Notch signaling has well defined roles in the assembly of arterial walls and in the development of the endothelium and smooth muscle of the vasculature. Hippo signaling regulates cellular growth in many tissues, and contributes to regulation of organ size, in addition to other functions. Here, we show that the Notch and Hippo pathways converge to regulate smooth muscle differentiation of neural crest, which is critical for normal development of the aortic arch arteries and cranial vasculature during embryonic development. Neural crest specific deletion of the Hippo effectors Yap and Taz produces neural crest precursors that migrate normally, but fail to produce vascular smooth muscle, and Notch target genes such as Jagged1 fail to activate normally. We show that Yap is normally recruited to a tissue-specific Jagged1 enhancer by directly interacting with the Notch intracellular domain (NICD). The Yap-NICD complex is recruited to chromatin by the DNA-binding protein Rbp-J in a Tead-independent fashion. Thus, Hippo signaling can modulate Notch signaling outputs, and components of the Hippo and Notch pathways physically interact. Convergence of Hippo and Notch pathways by the mechanisms described here may be relevant to the function of these signaling cascades in many tissues and in diseases such as cancer.

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The Induction of Yes-Associated Protein Expression After Arterial Injury Is Crucial for Smooth Muscle Phenotypic Modulation and Neointima Formation

Cited by 105 publications

References 32 publications

Thromboxane A2 Activates YAP/TAZ Protein to Induce Vascular Smooth Muscle Cell Proliferation and Migration

Thromboxane A2 Activates YAP/TAZ Protein to Induce Vascular Smooth Muscle Cell Proliferation and Migration

Flow-dependent YAP/TAZ activities regulate endothelial phenotypes and atherosclerosis

Hippo signaling is required for Notch-dependent smooth muscle differentiation of neural crest

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