Mural Cell SDF1 Signaling Is Associated with the Pathogenesis of Pulmonary Arterial Hypertension DOI
Ke Yuan, Yu Liu, Yue Zhang

et al.

American Journal of Respiratory Cell and Molecular Biology, Journal Year: 2020, Volume and Issue: 62(6), P. 747 - 759

Published: Feb. 21, 2020

Pulmonary artery smooth muscle cells (PASMCs) and pericytes are NG2+ mural that provide structural support to pulmonary arteries capillaries. In arterial hypertension (PAH), both cell types contribute PA muscularization, but whether similar mechanisms responsible for their behavior is unknown. RNA-seq was used compare the gene profile of PASMCs from PAH healthy lungs. NG2-Cre-ER mice were generate NG2-selective reporter (NG2tdT) lineage identification tamoxifen-inducible SDF1 knockout (SDF1NG2-KO). Hierarchical clustering data demonstrated genetic highly similar. Cellular staining studies on NG2tdT in chronic hypoxia showed that, PAH, tdT+ accumulate muscularized microvessels demonstrate significant upregulation SDF1, a chemokine involved chemotaxis angiogenesis. Compared with control mice, SDF1NG2-KO had reduced muscularization lower abundance around microvessels. stimulation induced greater contractility impaired capacity establish endothelial-pericyte communications. contrast, knockdown pericyte improved associate vascular tubes coculture. upregulated associated muscularization. Targeting could help prevent and/or reverse PAH.

Language: Английский

Resveratrol: Mechanistic and therapeutic perspectives in pulmonary arterial hypertension DOI
Elaheh Mirhadi, Basil D. Roufogalis, Maciej Banach

et al.

Pharmacological Research, Journal Year: 2020, Volume and Issue: 163, P. 105287 - 105287

Published: Nov. 3, 2020

Language: Английский

Citations

71
Oxidative Stress and Antioxidative Therapy in Pulmonary Arterial Hypertension DOI Creative Commons
Dan Xu,

Ya‐Hui Hu,

Xue Gou

et al.

Molecules, Journal Year: 2022, Volume and Issue: 27(12), P. 3724 - 3724

Published: June 9, 2022

Pulmonary arterial hypertension (PAH) is clinically characterized by a progressive increase in pulmonary artery pressure, followed right ventricular hypertrophy and subsequently heart failure. The underlying mechanism of PAH includes endothelial dysfunction intimal smooth muscle proliferation. Numerous studies have shown that oxidative stress critical the pathophysiology involves changes reactive oxygen species (ROS), nitrogen (RNS), nitric oxide (NO) signaling pathways. Disrupted ROS NO pathways cause proliferation cells (PAECs) vascular (PASMCs), resulting DNA damage, metabolic abnormalities, remodeling. Antioxidant treatment has become main area research for PAH. This review mainly introduces pathogenesis antioxidative therapies explains why targeting valid strategy treatment.

Language: Английский

Citations

45
New Drugs and Therapies in Pulmonary Arterial Hypertension DOI Open Access
Aangi J. Shah,

Taylor Beckmann,

Mounica Vorla

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5850 - 5850

Published: March 19, 2023

Pulmonary arterial hypertension is a chronic, progressive disorder of the pulmonary vasculature with associated and cardiac remodeling. PAH was uniformly fatal disease until late 1970s, but advent targeted therapies, life expectancy patients has now considerably improved. Despite these advances, inevitably remains significant morbidity mortality. Thus, there still an unmet need for development new drugs other interventional therapies treatment PAH. One shortcoming currently approved vasodilator that they do not target or reverse underlying pathogenesis process itself. A large body evidence evolved in past two decades clarifying role genetics, dysregulation growth factors, inflammatory pathways, mitochondrial dysfunction, DNA damage, sex hormones, neurohormonal iron deficiency This review focuses on newer targets modify pathways as well novel

Language: Английский

Citations

36
ATP13A3 variants promote pulmonary arterial hypertension by disrupting polyamine transport DOI Creative Commons
Bin Liu, Mujahid Azfar, Ekaterina Legchenko

et al.

Cardiovascular Research, Journal Year: 2024, Volume and Issue: 120(7), P. 756 - 768

Published: April 16, 2024

Potential loss-of-function variants of ATP13A3, the gene encoding a P5B-type transport ATPase undefined function, were recently identified in patients with pulmonary arterial hypertension (PAH). ATP13A3 is implicated polyamine but its function has not been fully elucidated. In this study, we sought to determine biological vascular endothelial cells (ECs) and how PAH-associated may contribute disease pathogenesis.

Language: Английский

Citations

12
HDAC6: A Novel Histone Deacetylase Implicated in Pulmonary Arterial Hypertension DOI Creative Commons
Olivier Boucherat,

Sophie Chabot,

Roxane Paulin

et al.

Scientific Reports, Journal Year: 2017, Volume and Issue: 7(1)

Published: June 27, 2017

Pulmonary arterial hypertension (PAH) is a vascular remodeling disease with limited therapeutic options. Although exposed to stressful conditions, pulmonary artery (PA) smooth muscle cells (PASMCs) exhibit "cancer-like" pro-proliferative and anti-apoptotic phenotype. HDAC6 cytoplasmic histone deacetylase regulating multiple pro-survival mechanisms overexpressed in response stress cancer cells. Due the similarities between PAH, we hypothesized that expression increased PAH-PASMCs face allowing them survive proliferate, thus contributing PAH. We found significantly up-regulated lungs, distal PAs, isolated PASMCs from PAH patients animal models. Inhibition of reduced PAH-PASMC proliferation resistance apoptosis vitro sparing control Mechanistically, demonstrated maintains Ku70 hypoacetylated state, blocking translocation Bax mitochondria preventing apoptosis. In vivo, pharmacological inhibition improved established two experimental models can be safely given combination currently approved therapies. Moreover, Hdac6 deficient mice were partially protected against chronic hypoxia-induced hypertension. Our study shows for first time implicated development represents new promising target improve

Language: Английский

Citations

87
Implication of Inflammation and Epigenetic Readers in Coronary Artery Remodeling in Patients With Pulmonary Arterial Hypertension DOI Open Access
Jolyane Meloche,

Marie-Claude Lampron,

Valérie Nadeau

et al.

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2017, Volume and Issue: 37(8), P. 1513 - 1523

Published: May 5, 2017

Pulmonary arterial hypertension (PAH) is a vascular disease not restricted to the lungs. Many signaling pathways described in PAH are also of importance other remodeling diseases, such as coronary artery (CAD). Intriguingly, CAD 4× more prevalent compared with global population, suggesting link between these 2 diseases. Both and associated sustained inflammation smooth muscle cell proliferation/apoptosis imbalance we demonstrated that this phenotype is, part, because miR-223/DNA damage/Poly[ADP-ribose] polymerase 1/miR-204 axis activation subsequent bromodomain protein 4 (BRD4) overexpression. Interestingly, BRD4 trigger for calcification processes, both which important CAD. Thus, hypothesize influences development CAD.PAH was significant arteries human experimental models disease. As observed distal pulmonary arteries, patients exhibited increased DNA damage, inflammation, In vitro, using cells from PAH, non-PAH-non-CAD patients, showed proliferation suppressed apoptosis BRD4-dependent manner. vivo, improvement by inhibitor reduction interleukin-6 expression.Overall, study demonstrates expression patient contributes comorbidity development.

Language: Английский

Citations

82
Translational Advances in the Field of Pulmonary Hypertension.Translating MicroRNA Biology in Pulmonary Hypertension. It Will Take More Than “miR” Words DOI
Hyung J. Chun, Sébastien Bonnet, Stephen Y. Chan

et al.

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2016, Volume and Issue: 195(2), P. 167 - 178

Published: Sept. 20, 2016

Language: Английский

Citations

75
New and Emerging Therapies for Pulmonary Arterial Hypertension DOI
Edda Spiekerkoetter, Steven M. Kawut,

Vinicio A. de Jesús Pérez

et al.

Annual Review of Medicine, Journal Year: 2018, Volume and Issue: 70(1), P. 45 - 59

Published: Sept. 16, 2018

Pulmonary arterial hypertension (PAH) is a pulmonary vasculopathy that causes right ventricular dysfunction and exercise limitation progresses to death. New findings from translational studies have suggested alternative pathways for treatment. These avenues include sex hormones, genetic abnormalities DNA damage, elastase inhibition, metabolic dysfunction, cellular therapies, anti-inflammatory approaches. Both novel repurposed compounds with rationale preclinical experimental models human cells are now in clinical trials patients PAH. Findings these will elucidate the pathobiology of PAH may result clinically important improvements outcome.

Language: Английский

Citations

75
Oxidative Stress and Disease DOI Creative Commons

Rosngela F.F. de Araújo,

Danyelly Bruneska Gondim Martins,

Maria Amélia C.S.M. Borba

et al.

InTech eBooks, Journal Year: 2016, Volume and Issue: unknown

Published: Dec. 21, 2016

Typically in aerobic metabolism, organic compounds such as nucleic acids, proteins and lipids can undergo structural damage by oxidative reactions. This caused reactive oxygen/nitrogen species has been recognized “oxidative stress”. Despite the biological systems present efficient enzymatic nonenzymatic antioxidant systems, stress indicates a pro-oxidant/antioxidant imbalance favor of excessive generation free radicals or decrease removal rate. Various diseases cancer, diabetes, cardiovascular neurodegenerative clearly exemplify chronic stress. Therefore, it is important to consider that at low moderate ROS levels, can, for example, act signaling molecules support cell proliferation differentiation activate survival pathways response Correlations between disease should be carefully investigated order understand whether actually increases susceptibility particular opposite.

Language: Английский

Citations

70
The role of chemokines and chemokine receptors in pulmonary arterial hypertension DOI Open Access
Argen Mamazhakypov, Gayathri Viswanathan, Allan Lawrie

et al.

British Journal of Pharmacology, Journal Year: 2019, Volume and Issue: 178(1), P. 72 - 89

Published: Aug. 10, 2019

Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary artery remodelling leading to increased right ventricular pressure overload, which results in heart failure and premature death. Inflammation plays a central role the development of PAH, recruitment function immune cells are tightly regulated chemotactic cytokines called chemokines. A number studies have shown that progression PAH associated with dysregulated expression several chemokines chemokine receptors vasculature. Moreover, some differentially pressure‐overloaded ventricle. Recent tested efficacy pharmacological agents targeting for their effects on suggesting these could serve as useful therapeutic targets. In this review, we provide recent insights into RV opportunities roadblocks them. LINKED ARTICLES This article part themed issue Risk factors, comorbidities, comedications cardioprotection. To view other articles section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc

Language: Английский

Citations

56