Yes‐associated protein mediates angiotensin <scp>II</scp>‐induced vascular smooth muscle cell phenotypic modulation and hypertensive vascular remodelling

Miao, Lin; Yuan, Wei; Su, Ziyi; Lin, Caina; Huang, Tao; Chen, Yangxin; Wang, Jingfeng

doi:10.1111/cpr.12517

Cited by 29 publications

(21 citation statements)

References 36 publications

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“…Mice treated with angiotensin II show YAP up-regulation in their blood vessels. Interestingly, disrupting the YAP–TEAD interaction with verteporfin inhibits Ang II-induced vascular remodeling in mice [115].…”

Section: Roles Of Yap/taz In Pathological Angiogenesismentioning

confidence: 99%

The Role of YAP and TAZ in Angiogenesis and Vascular Mimicry

Azad

Ghahremani

Yang

2019

Cells

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Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a physiological process that begins in utero and continues throughout life in both good health and disease. Understanding the underlying mechanism in angiogenesis could uncover a new therapeutic approach in pathological angiogenesis. Since its discovery, the Hippo signaling pathway has emerged as a key player in controlling organ size and tissue homeostasis. Recently, new studies have discovered that Hippo and two of its main effectors, Yes-associated protein (YAP) and its paralog transcription activator with PDZ binding motif (TAZ), play critical roles during angiogenesis. In this review, we summarize the mechanisms by which YAP/TAZ regulate endothelial cell shape, behavior, and function in angiogenesis. We further discuss how YAP/TAZ function as part of developmental and pathological angiogenesis. Finally, we review the role of YAP/TAZ in tumor vascular mimicry and propose directions for future work.

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Section: Roles Of Yap/taz In Pathological Angiogenesismentioning

confidence: 99%

The Role of YAP and TAZ in Angiogenesis and Vascular Mimicry

Azad

Ghahremani

Yang

2019

Cells

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“…As shown in Figure 6 , kahweol inhibited Ang II-induced YAP expression, and rCTGF reversed the kahweol effect. CTGF is known as a target gene of YAP [ 41 , 42 ], and Lin et al showed that YAP has a pivotal role in Ang II-induced hypertensive vascular remodeling and phenotypic switching in VSMCs [ 43 ]. Lachowski et al showed that FAK controls the mechanical activation of YAP, which is required for durotaxis in human hepatic stellate cells [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…showed that YAP has a pivotal role in Ang II-induced hypertensive vascular remodeling and phenotypic switching in VSMCs [43]. Lachowski et al showed that FAK controls the mechanical activation of YAP, which is required for durotaxis in human hepatic stellate cells [30].…”

Section: Discussionmentioning

confidence: 99%

Kahweol, a Diterpenoid Molecule, Inhibits CTGF-Dependent Synthetic Phenotype Switching and Migration in Vascular Smooth Muscle Cells

2021

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Vascular smooth muscle cell (VSMC) phenotype switching from contractile to synthetic is essential for proliferation and migration in vascular pathophysiology. Connective tissue growth factor (CTGF) is a matricellular protein involved in cell adhesion, migration, and proliferation. Kahweol, a diterpene molecule in arabica coffee beans, has been reported to have anti-inflammatory, antiproliferative, and apoptotic effects in many cells. However, in VSMCs, the effects of kahweol on CTGF activities have not been investigated. Thus, in this study, the effects and associated mechanisms of kahweol in CTGF-dependent phenotype switching and migration in VSMCs were examined. Experiments were performed on primary rat aortic smooth muscle cells and a rat VSMC line, A7r5. Western blot analysis was used to determine the protein levels. The mRNA levels of synthetic markers were measured by qRT-PCR. Migration of VSMCs was evaluated by wound healing and transwell assays. Kahweol reduced the angiotensin II (Ang II)-induced CTGF expression. Further, kahweol inhibited expressions of synthetic phenotype markers of VSMC. The kahweol-reduced synthetic marker protein levels were reversed by the administration of rCTGF. However, expressions of contractile phenotype markers of VSMC were not affected. Kahweol suppressed Ang II-stimulated VSMC migration. Moreover, kahweol downregulated Ang II-induced p-FAK, p-Erk, and Yes-associated protein (YAP) protein expressions. Taken together, in Ang II-stimulated VSMCs, kahweol inhibited CTGF-dependent synthetic phenotype switching and migration, with focal adhesion kinase (FAK), Erk, and YAP involved in the underlying mechanisms of the kahweol effects. These results suggest that kahweol has a potential as a therapeutic agent to inhibit CTGF, which is a molecular target in sclerogenic vascular disease.

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“…YAP/TEAD plays a critical role in the phenotypic switching of VSMCs and subsequent vascular remodeling [3][4][5]. YAP/TEAD is also activated by well-known VSMC phenotypic switch-inducing factors such as PDGF-BB [4], angiotensin II [49], and thromboxane A2 [50]. Inhibition of YAP/TEAD activity alleviates VSMC phenotypic transformation in vitro and vascular remodeling in vivo.…”

Section: Discussionmentioning

confidence: 99%

Homeobox A4 suppresses vascular remodeling by repressing YAP / TEAD transcriptional activity

et al. 2020

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The Hippo signaling pathway is involved in the pathophysiology of various cardiovascular diseases. Yes‐associated protein (YAP) and transcriptional enhancer activator domain (TEAD) transcriptional factors, the main transcriptional complex of the Hippo pathway, were recently identified as modulators of phenotypic switching of vascular smooth muscle cells (VSMCs). However, the intrinsic regulator of YAP/TEAD‐mediated gene expressions involved in vascular pathophysiology remains to be elucidated. Here, we identified Homeobox A4 (HOXA4) as a potent repressor of YAP/TEAD transcriptional activity using lentiviral shRNA screen. Mechanistically, HOXA4 interacts with TEADs and attenuates YAP/TEAD‐mediated transcription by competing with YAP for TEAD binding. We also clarified that the expression of HOXA4 is relatively abundant in the vasculature, especially in VSMCs. In vitro experiments in human VSMCs showed HOXA4 maintains the differentiation state of VSMCs via inhibition of YAP/TEAD‐induced phenotypic switching. We generated Hoxa4‐deficient mice and confirmed the downregulation of smooth muscle‐specific contractile genes and the exacerbation of vascular remodeling after carotid artery ligation in vivo. Our results demonstrate that HOXA4 is a repressor of VSMC phenotypic switching by inhibiting YAP/TEAD‐mediated transcription.

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Yes‐associated protein mediates angiotensin II‐induced vascular smooth muscle cell phenotypic modulation and hypertensive vascular remodelling

Abstract: Yes-associated protein mediated angiotensin II-induced VSMCs phenotypic modulation and vascular remodelling. YAP is a potential therapeutic target for HVR beyond blood pressure control.

Cited by 29 publications

References 36 publications

The Role of YAP and TAZ in Angiogenesis and Vascular Mimicry

The Role of YAP and TAZ in Angiogenesis and Vascular Mimicry

Kahweol, a Diterpenoid Molecule, Inhibits CTGF-Dependent Synthetic Phenotype Switching and Migration in Vascular Smooth Muscle Cells

Homeobox A4 suppresses vascular remodeling by repressing YAP / TEAD transcriptional activity

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