Pulmonary arterial hypertension

Luna‐López, Raquel; Martín, Alicia Ruiz; Subías, Pilar Escribano

doi:10.1016/j.medcle.2022.05.010

Cited by 14 publications

(10 citation statements)

References 28 publications

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“…The hallmark of HPH is a mean pulmonary artery pressure greater than 25 mmHg at rest, leading to severe progressive lung disease, right heart failure, and premature death due to exposure to hypoxia ( Luna-López et al, 2022 ). The World Health Organization (WHO) classifies PH into five clinical subtypes based on etiology.…”

Section: The Role Of Hypoxia-induced Mitochondrial Dysregulation In Hphmentioning

confidence: 99%

Mitochondria in hypoxic pulmonary hypertension, roles and the potential targets

Geng

Zhang

et al. 2023

Front. Physiol.

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Mitochondria are the centrol hub for cellular energy metabolisms. They regulate fuel metabolism by oxygen levels, participate in physiological signaling pathways, and act as oxygen sensors. Once oxygen deprived, the fuel utilizations can be switched from mitochondrial oxidative phosphorylation to glycolysis for ATP production. Notably, mitochondria can also adapt to hypoxia by making various functional and phenotypes changes to meet the demanding of oxygen levels. Hypoxic pulmonary hypertension is a life-threatening disease, but its exact pathgenesis mechanism is still unclear and there is no effective treatment available until now. Ample of evidence indicated that mitochondria play key factor in the development of hypoxic pulmonary hypertension. By hypoxia-inducible factors, multiple cells sense and transmit hypoxia signals, which then control the expression of various metabolic genes. This activation of hypoxia-inducible factors considered associations with crosstalk between hypoxia and altered mitochondrial metabolism, which plays an important role in the development of hypoxic pulmonary hypertension. Here, we review the molecular mechanisms of how hypoxia affects mitochondrial function, including mitochondrial biosynthesis, reactive oxygen homeostasis, and mitochondrial dynamics, to explore the potential of improving mitochondrial function as a strategy for treating hypoxic pulmonary hypertension.

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Section: The Role Of Hypoxia-induced Mitochondrial Dysregulation In Hphmentioning

confidence: 99%

Mitochondria in hypoxic pulmonary hypertension, roles and the potential targets

Geng

Zhang

et al. 2023

Front. Physiol.

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“…PAH is a rare, progressive and devastating disease in which there is high blood pressure due to thickening and narrowing of the small arteries in the lungs (Refs 122 , 123 ). The blockage in the pulmonary vessels may progress to right-side heart failure which is the primary cause of high morbidity and mortality associated with PAH (Refs 124 , 125 , 126 ). At the cellular level, the main changes in PAH include proliferation of fibroblasts, infiltration of immune cells and proliferation of PASMCs (Refs 125 , 127 , 128 , 129 , 130 ).…”

Section: Notch3 Signalling and Acute Or Chronic Lung Diseasementioning

confidence: 99%

The emerging role of NOTCH3 receptor signalling in human lung diseases

Bodas

Bharathiraja

Karmouty‐Quintana

et al. 2022

Expert Rev. Mol. Med.

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The mammalian respiratory system or lung is a tree-like branching structure, and the main site of gas exchange with the external environment. Structurally, the lung is broadly classified into the proximal (or conducting) airways and the distal alveolar region, where the gas exchange occurs. In parallel with the respiratory tree, the pulmonary vasculature starts with large pulmonary arteries that subdivide rapidly ending in capillaries adjacent to alveolar structures to enable gas exchange. The NOTCH signalling pathway plays an important role in lung development, differentiation and regeneration post-injury. Signalling via the NOTCH pathway is mediated through activation of four NOTCH receptors (NOTCH1-4), with each receptor capable of regulating unique biological processes. Dysregulation of the NOTCH pathway has been associated with development and pathophysiology of multiple adult acute and chronic lung diseases. This includes accumulating evidence that alteration of NOTCH3 signalling plays an important role in the development and pathogenesis of chronic obstructive pulmonary disease, lung cancer, asthma, idiopathic pulmonary fibrosis and pulmonary arterial hypertension. Herein, we provide a comprehensive summary of the role of NOTCH3 signalling in regulating repair/regeneration of the adult lung, its association with development of lung disease and potential therapeutic strategies to target its signalling activity.

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“…A primary contributor to the onset of PH is increased pulmonary vascular resistance due to pathological changes such as persistent vasoconstriction and excessive pulmonary vascular remodeling (Hoeper et al 2013 ; Luna-Lopez et al 2022 ; Naeije et al 2022 ). The proliferation of pulmonary artery smooth muscle cells (PASMCs) is the basis of this pathological change.…”

Section: Introductionmentioning

confidence: 99%

Nupr1-mediated vascular smooth muscle cell phenotype transformation involved in methamphetamine induces pulmonary hypertension

Zhou,

Guo,

et al. 2024

Cell Biol Toxicol

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Aims Nuclear protein 1 (Nupr1) is a multifunctional stress-induced protein involved in the regulation of tumorigenesis, apoptosis, and autophagy. However, its role in pulmonary hypertension (PH) after METH exposure remains unexplored. In this study, we aimed to investigate whether METH can induce PH and describe the role and mechanism of Nupr1 in the development of PH. Methods and results Mice were made to induce pulmonary hypertension (PH) upon chronic intermittent treatment with METH. Their right ventricular systolic pressure (RVSP) was measured to assess pulmonary artery pressure. Pulmonary artery morphometry was determined by H&E staining and Masson staining. Nupr1 expression and function were detected in human lungs, mice lungs exposed to METH, and cultured pulmonary arterial smooth muscle cells (PASMCs) with METH treatment. Our results showed that chronic intermittent METH treatment successfully induced PH in mice. Nupr1 expression was increased in the cultured PASMCs, pulmonary arterial media from METH-exposed mice, and METH-ingested human specimens compared with control. Elevated Nupr1 expression promoted PASMC phenotype change from contractile to synthetic, which triggered pulmonary artery remodeling and resulted in PH formation. Mechanistically, Nupr1 mediated the opening of store-operated calcium entry (SOCE) by activating the expression of STIM1, thereby promoting Ca2+ influx and inducing phenotypic conversion of PASMCs. Conclusions Nupr1 activation could promote Ca2+ influx through STIM1-mediated SOCE opening, which promoted METH-induced pulmonary artery remodeling and led to PH formation. These results suggested that Nupr1 played an important role in METH-induced PH and might be a potential target for METH-related PH therapy. Graphical Abstract 1. Chronic intermittent methamphetamine exposure can induce the development of pulmonary arterial hypertension. 2. Nupr1 plays a key role in the development of methamphetamine-related pulmonary arterial hypertension. 3. Nupr1 mediates PASMCs phenotypic transformation via STIM1signal axis, which results in the development of methamphetamine-related pulmonary arterial hypertension.

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Pulmonary arterial hypertension

Cited by 14 publications

References 28 publications

Mitochondria in hypoxic pulmonary hypertension, roles and the potential targets

Mitochondria in hypoxic pulmonary hypertension, roles and the potential targets

The emerging role of NOTCH3 receptor signalling in human lung diseases

Nupr1-mediated vascular smooth muscle cell phenotype transformation involved in methamphetamine induces pulmonary hypertension

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