Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension

Bertero, Thomas; Oldham, William M.; Cottrill, Katherine A.; Pisano, Sabrina; Vanderpool, Rebecca; Yu, Qingzhen; Zhao, Jingsi; Tai, Yi-Yin; Tang, Ying; Zhang, Yingyi; Rehman, Sofiya; Sugahara, Masataka; Qi, Zhi Wei; Gorcsan, John; Vargas, Sara O.; Saggar, Rajan; Saggar, Rajeev; Wallace, W. Dean; Ross, David J.; Haley, Kathleen J.; Waxman, Aaron B.; Parikh, Victoria N.; Marco, Teresa De; Hsue, Priscilla Y.; Morris, Alison; Simon, Marc A.; Norris, Karen A.; Gaggioli, Cédric; Loscalzo, Joseph; Fessel, Joshua P.; Chan, Stephen Y.

doi:10.1172/jci86387

Cited by 329 publications

(367 citation statements)

References 55 publications

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“…Two recent studies by BERTERO and co-workers [9,10] have provided insights into the molecular pathways involved in vascular stiffening in PAH, and have indicated a role for the co-transcription factors YAP/TAZ (Yes-associated protein/transcriptional coactivator with PDZ-binding motif ) and the microRNA-130/301 family (miR-130/301). In 2015, BERTERO et al [9] demonstrated that ECM remodelling activates YAP/TAZ in pulmonary vascular cells.…”

Section: Vascular Stiffnessmentioning

confidence: 99%

Pathobiology of pulmonary arterial hypertension: understanding the roads less travelled

Hemnes

Humbert

2017

Eur Respir Rev

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The pathobiology of pulmonary arterial hypertension (PAH) is complex and incompletely understood. Although three pathogenic pathways have been relatively well characterised, it is widely accepted that dysfunction in a multitude of other cellular processes is likely to play a critical role in driving the development of PAH. Currently available therapies, which all target one of the three well-characterised pathways, provide significant benefits for patients; however, PAH remains a progressive and ultimately fatal disease. The development of drugs to target alternative pathogenic pathways is, therefore, an attractive proposition and one that may complement existing treatment regimens to improve outcomes for patients. Considerable research has been undertaken to identify the role of the less well-understood pathways and in this review we will highlight some of the key discoveries and the potential for utility as therapeutic targets.

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Section: Vascular Stiffnessmentioning

confidence: 99%

Pathobiology of pulmonary arterial hypertension: understanding the roads less travelled

Hemnes

Humbert

2017

Eur Respir Rev

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“…Separately, the miR-130/301 family has been found to modulate extracellular matrix stiffening in PAAFs (31) via interfacing with the transcriptional coactivators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif). The connection between YAP/TAZ and this miRNA family has led to additional understanding of the broader links among pulmonary vascular stiffness, glutamine metabolism, and proliferation (32,33).…”

Section: Metabolism and Proliferationmentioning

confidence: 99%

Translational Advances in the Field of Pulmonary Hypertension.Translating MicroRNA Biology in Pulmonary Hypertension. It Will Take More Than “miR” Words

Chun

Bonnet²,

Chan

2017

Am J Respir Crit Care Med

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“…[1][2][3][4] [1] is a progressive disease of pulmonary arterial circulation, leading to progressive increase in pulmonary vascular resistance (PVR) and pulmonary artery pressure (PAP) and results in end-stage right heart failure and death. Decompensated right ventricular (RV) failure carries very high risk of unfavorable outcome and is associated with higher mortality than decompensated left heart failure [2].…”

Section: Introductionmentioning

confidence: 99%

“…Two main factors play an important role in triggering maladaptive changes in RV morphology: hypoxia and increased vascular and perivascular stiffness. A mechanical stimulus in experimental models proves to be one of the key factors, by which cellular proliferation and migration is induced in pulmonary arterial wall imposing subsequently on RV [4]. Vascular and extracellular stiffness is directly linked with pulmonary arterial compliance, a measure of flow volume and pressure in pulmonary circulation that describes pulsatile component of afterload [5].…”

Section: Introductionmentioning

confidence: 99%

Pulmonary artery pressure matters – how to efficiently improve survival in pulmonary arterial hypertension (RCD code: II‐1A.1)

Matsubara

Błaszczak

Podolec

et al. 2017

Journal of Rare Cardiovascular Diseases

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Please cite this article: Matsubara H, Blaszczak P, Podolec P, et al. Pulmonary artery pressure matters -how to efficiently improve survival in pulmonary arterial hypertension. AbstractPulmonary arterial hypertension is a disease characterized by poor prognosis despite treatment. Even in a modern era of pharmacotherapy there is a strong need to further improve survival of patients. The current therapeutic strategies do not offer a real break-through in terms of reducing mortality. In a search for better efficacy of treatment we discuss a strategy based on lowering pulmonary artery pressure as much as possible with epoprostenol in monotherapy or in combination. Epoprostenol with bosentan is an effective tool in achieving this goal. A rapid up-titration regardless of maximum epoprostenol dose achieved gives additional long-term benefit. Practical issues related to such modality of treatment are also discussed. JRCD 2017; 3 (4): 110-115

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Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension

Cited by 329 publications

References 55 publications

Pathobiology of pulmonary arterial hypertension: understanding the roads less travelled

Pathobiology of pulmonary arterial hypertension: understanding the roads less travelled

Translational Advances in the Field of Pulmonary Hypertension.Translating MicroRNA Biology in Pulmonary Hypertension. It Will Take More Than “miR” Words

Pulmonary artery pressure matters – how to efficiently improve survival in pulmonary arterial hypertension (RCD code: II‐1A.1)

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