&lt;p&gt;Paeoniflorin Ameliorates Chronic Hypoxia/SU5416-Induced Pulmonary Arterial Hypertension by Inhibiting Endothelial-to-Mesenchymal Transition&lt;/p&gt;

Yu, Min; Peng, Liyao; Liu, Ping; Yang, Mingxia; Zhou, Hong; Ding, Yirui; Wang, Jingjing; Huang, Wen; Tan, Qian; Wang, Yanli; Xie, Wei; Kong, Hui; Wang, Hong

doi:10.2147/dddt.s235207

Cited by 19 publications

(12 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In many cases, molecular mechanisms and intermediate players connecting the two processes have not been detailed, and their elucidation would be beneficial for the field at large. Nonetheless, with that need in mind, by presenting compelling data arguing for utilization of BMP signaling restoration strategies targeting EndMT in the treatment of PH (148,202), and offering a number of mechanistic insights into the BMPR-mediated control over EndMT progression (74,102,163,202), the works discussed above do make a persuasive argument for the development of therapeutics aimed at the reversal of PAH-associated EndMT and pave a way for future explorations (198). Finally, the embryonic origin and developmental importance of both BMP signaling [reviewed in Wang et al (186)], EndMT (115,177), and their connections (109,118) suggest an early deep-rooted interconnection between the two processes that may be subject to temporal regulation and perhaps also suggest a critical coregulation in cell fate determination.…”

Section: The Role Of Hypoxia In Ph-associated Endmtmentioning

confidence: 99%

Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension

Gorelova

Berman

Ghouleh

2021

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Endothelial-to-mesenchymal transition (EndMT) is a process that encompasses extensive transcriptional reprogramming of activated endothelial cells leading to a shift toward mesenchymal cellular phenotypes and functional responses. Initially observed in the context of embryonic development, in the last few decades EndMT is increasingly recognized as a process that contributes to a variety of pathologies in the adult organism. Within the settings of cardiovascular biology, EndMT plays a role in various diseases, including atherosclerosis, heart valvular disease, cardiac fibrosis, and myocardial infarction. EndMT is also being progressively implicated in development and progression of pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH). This review covers the current knowledge about EndMT in PH and PAH, and provides comprehensive overview of seminal discoveries. Topics covered include evidence linking EndMT to factors associated with PAH development, including hypoxia responses, inflammation, dysregulation of bone-morphogenetic protein receptor 2 (BMPR2), and redox signaling. This review amalgamates these discoveries into potential insights for the identification of underlying mechanisms driving EndMT in PH and PAH, and discusses future directions for EndMT-based therapeutic strategies in disease management. Antioxid. Redox Signal. 34, 891-914.

show abstract

Section: The Role Of Hypoxia In Ph-associated Endmtmentioning

confidence: 99%

Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension

Gorelova

Berman

Ghouleh

2021

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

show abstract

“…Determining how to improve cellular plasticity and muscularization in PASMCs to reverse pulmonary vascular remodelling may represent a new potential perspective for the treatment of PAH in future studies. Additionally, multiple studies have also demonstrated that the endothelial–mesenchymal transition (EndMT) caused by hypoxia was also a vital factor for pulmonary vascular remodelling in rats [ 23 , 24 ]. At present, due to cardiopulmonary pathophysiology also contributing to neuroinflammation, altered gastrointestinal function, and increased bone marrow-derived cells, PAH could be considered a brain–gut–lung systemic disease [ 25 ].…”

Section: Pathophysiology Of Pahmentioning

confidence: 99%

Bioactivities and mechanisms of natural medicines in the management of pulmonary arterial hypertension

Zhang

Xiao

et al. 2022

Chin Med

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) is a progressive and rare disease without obvious clinical symptoms that shares characteristics with pulmonary vascular remodeling. Right heart failure in the terminal phase of PAH seriously threatens the lives of patients. This review attempts to comprehensively outline the current state of knowledge on PAH its pathology, pathogenesis, natural medicines therapy, mechanisms and clinical studies to provide potential treatment strategies. Although PAH and pulmonary hypertension have similar pathological features, PAH exhibits significantly elevated pulmonary vascular resistance caused by vascular stenosis and occlusion. Currently, the pathogenesis of PAH is thought to involve multiple factors, primarily including genetic/epigenetic factors, vascular cellular dysregulation, metabolic dysfunction, even inflammation and immunization. Yet many issues regarding PAH need to be clarified, such as the “oestrogen paradox”. About 25 kinds monomers derived from natural medicine have been verified to protect against to PAH via modulating BMPR2/Smad, HIF-1α, PI3K/Akt/mTOR and eNOS/NO/cGMP signalling pathways. Yet limited and single PAH animal models may not corroborate the efficacy of natural medicines, and those natural compounds how to regulate crucial genes, proteins and even microRNA and lncRNA still need to put great attention. Additionally, pharmacokinetic studies and safety evaluation of natural medicines for the treatment of PAH should be undertaken in future studies. Meanwhile, methods for validating the efficacy of natural drugs in multiple PAH animal models and precise clinical design are also urgently needed to promote advances in PAH. Graphical Abstract

show abstract

“…Recently, it has been demonstrated that the monoterpene glycoside paeoniflorin, a molecule with endothelial protection and antifibrotic properties, significantly prevented chronic hypoxia/SU5416-induced PAH in rats, with a therapeutic effect likely being related to its capability to inhibit EndoMT in lung arterial ECs [ 209 ].…”

Section: Main Molecular Pathways Driving Myofibroblast Differentiation From Vascular Wall Residing Cells In Systemic Sclerosis and Relatementioning

confidence: 99%

New Insights into Profibrotic Myofibroblast Formation in Systemic Sclerosis: When the Vascular Wall Becomes the Enemy

Romano

Rosa

Fioretto

et al. 2021

Life

View full text Add to dashboard Cite

In systemic sclerosis (SSc), abnormalities in microvessel morphology occur early and evolve into a distinctive vasculopathy that relentlessly advances in parallel with the development of tissue fibrosis orchestrated by myofibroblasts in nearly all affected organs. Our knowledge of the cellular and molecular mechanisms underlying such a unique relationship between SSc-related vasculopathy and fibrosis has profoundly changed over the last few years. Indeed, increasing evidence has suggested that endothelial-to-mesenchymal transition (EndoMT), a process in which profibrotic myofibroblasts originate from endothelial cells, may take center stage in SSc pathogenesis. While in arterioles and small arteries EndoMT may lead to the accumulation of myofibroblasts within the vessel wall and development of fibroproliferative vascular lesions, in capillary vessels it may instead result in vascular destruction and formation of myofibroblasts that migrate into the perivascular space with consequent tissue fibrosis and microvessel rarefaction, which are hallmarks of SSc. Besides endothelial cells, other vascular wall-resident cells, such as pericytes and vascular smooth muscle cells, may acquire a myofibroblast-like synthetic phenotype contributing to both SSc-related vascular dysfunction and fibrosis. A deeper understanding of the mechanisms underlying the differentiation of myofibroblasts inside the vessel wall provides the rationale for novel targeted therapeutic strategies for the treatment of SSc.

show abstract

<p>Paeoniflorin Ameliorates Chronic Hypoxia/SU5416-Induced Pulmonary Arterial Hypertension by Inhibiting Endothelial-to-Mesenchymal Transition</p>

Cited by 19 publications

References 40 publications

Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension

Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension

Bioactivities and mechanisms of natural medicines in the management of pulmonary arterial hypertension

New Insights into Profibrotic Myofibroblast Formation in Systemic Sclerosis: When the Vascular Wall Becomes the Enemy

Contact Info

Product

Resources

About