Mitochondrial dysfunction in pulmonary arterial hypertension

Zhang, Weiwei; Liu, Bo; Wang, Shaobin; Zhang, Hengli; He, Lin; Wang, Pan; Dong, Mingqing

doi:10.3389/fphys.2022.1079989

Cited by 9 publications

(6 citation statements)

References 168 publications

(206 reference statements)

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“…Many studies have shown that the development of PAH is closely related to mitochondrial dysfunction, which includes the tricarboxylic acid cycle, redox homeostasis, enhanced glycolysis, increased ROS expression etc. ( 13 , 59 ). The hypertrophy in the RV seems to be associated with a decreased mitochondrial glucose oxidation and a glycolytic phenotype ( 60 ).…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

“…Patients with diabetes have pulmonary vascular complications, and this occurs mainly because glucose is the major energy source for maintaining vascular contraction. Glucose metabolism in blood vessels is mostly related to glucose anaerobic fermentation, and a chronic metabolic disorder in this process can damage and increase the mitochondria division in vascular endothelial, and SMCs, affecting the tone of vessels ( 59 ).…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

“…When the stress is high or chronic, the ER can send signals to the mitochondria to start programmed cell death (apoptosis), showing the importance of this organelle in this process ( 68 ). However, abnormal mitochondria in PAH can suppress this event, and increase vascular remodeling and heart failure ( 59 ).…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

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Pulmonary hypertension and insulin resistance: a mechanistic overview

Zanotto,

Gonçalves,

Saad

2024

Front. Endocrinol.

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Pulmonary arterial hypertension (PAH) is a vascular remodeling disease, characterized by increased blood pressure levels in pulmonary circulation, leading to a restriction in the circulation flow and heart failure. Although the emergence of new PAH therapies has increased survival rates, this disease still has a high mortality and patients that receive diagnosis die within a few years. The pathogenesis of PAH involves multiple pathways, with a complex interaction of local and distant cytokines, hormones, growth factors, and transcription factors, leading to an inflammation that changes the vascular anatomy in PAH patients. These abnormalities involve more than just the lungs, but also other organs, and between these affected organs there are different metabolic dysfunctions implied. Recently, several publications demonstrated in PAH patients a disturbance in glucose metabolism, demonstrated by higher levels of glucose, insulin, and lipids in those patients. It is possible that a common molecular mechanism can have a significant role in this connection. In this regard, this narrative review intends to focus on the recent papers that mainly discuss the molecular determinants between insulin resistance (IR) associated PAH, which included obesity subclinical inflammation induced IR, PPAR gamma and Adiponectin, BMPR2, mitochondrial dysfunction and endoplasmic reticulum stress. Therefore, the following review will summarize some of the existing data for IR associated PAH, focusing on the better understanding of PAH molecular mechanisms, for the development of new translational therapies.

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Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

See 1 more Smart Citation

Pulmonary hypertension and insulin resistance: a mechanistic overview

Zanotto,

Gonçalves,

Saad

2024

Front. Endocrinol.

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“…Studies have shown that mitochondrial dysfunction and DNA damage are involved in the remodeling of pulmonary vasculature and right ventricle in PAH. 72 73 Dilong (Pheretima), a Chinese herb used to soothe wind and relieve convulsions, mainly functions to clear heat and arrest convulsions, dredge collaterals, relieve asthma, and promote diuresis. Liu et al 74 found that the extract of Dilong (Pheretima) can downregulate the protein expression of NLRP3 in lung tissue of PAH rats, reduce oxidative stress and inflammation levels in pulmonary artery endothelial cells, alleviate apoptosis, improve mitochondrial functional damage, and thus inhibit pulmonary vascular remodeling and PAH.…”

Section: Research Status Of Traditional Chinese Medicine Regulation O...mentioning

confidence: 99%

Research Progress on Chinese Medicine Regulation of Mitochondrial Damage for Intervention in Respiratory System Diseases

Li,

Yang,

Qin

et al. 2024

Chinese medicine and natural products

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Mitochondria are important organelles in cells for energy production, and mitochondrial damage caused by various reasons is an important factor promoting disease progression. Mitochondrial damage involves structural damage and mitochondrial DNA damage, which are closely related to the occurrence and development of respiratory system diseases. In recent years, a large number of studies have confirmed the significant role of mitochondrial damage in the progression of respiratory system diseases, which may be an important target for the treatment of respiratory system diseases with traditional Chinese medicine (TCM). This article reviews the role of TCM in regulating mitochondrial damage for intervention in respiratory system diseases such as chronic obstructive pulmonary disease, lung cancer, pulmonary fibrosis, acute lung injury, asthma, and pneumonia, aiming to provide a basis for the study of the pathogenesis and drug action targets of respiratory system diseases.

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“…Moreover, cellular iron-loading is known to cause mitochondrial dysfunction enhancing intracellular reactive oxygen species (ROS) production, affecting intracellular cell signalling responses and ultimately cell fate (Rouault et al 2016). Throughout the literature, a role for mitochondrial dysfunction in PAH is emerging (Zhang et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

The hepcidin-ferroportin axis influences mitochondrial function, proliferation, and migration in pulmonary artery endothelial and smooth muscle cells

Issitt,

Toe,

Pedersen

et al. 2023

Preprint

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RationaleElevated circulating hepcidin levels have been reported in patients with pulmonary artery hypertension (PAH). Hepcidin has been shown to promote proliferation of human pulmonary artery smooth muscle cells (PASMCs) in vitro, suggesting a potential role in PAH pathogenesis. However, the role of human pulmonary artery endothelial cells (PAECs) as either a source of hepcidin, or the effect of hepcidin on PAECfunction has not previously been described.ObjectiveTo define the role of the hepcidin-ferroportin axis on the phenotype of pulmonary artery endothelial cellsMethods and resultsPAECs treated with hepcidin, or IL-6 were investigated for both ferroportin and hepcidin release and regulation with immunofluorescence, mRNA levels and cellular release assays. Effects of hepcidin on PASMC and PAEC mitochondrial function was investigated using immunofluorescence and seahorse assay. Migration and proliferation of PASMC treated with conditioned media from hPAEC treated with hepcidin was investigated using the Xcelligence system and other tools.PAECs express ferroportin; hepcidin treatment of PAECs results in mitochondrial iron accumulation and intracellular hepcidin biosynthesis and release. Conditioned media from hepcidin treated PAECs causes PASMCs to down regulate ferroportin expression whilst promoting migration and proliferation. Inhibition of hepcidin in PAEC conditioned media limits these responses. PASMC cellular and mitochondrial iron retention are associated with migratory and proliferative responses.ConclusionsThe Hepcidin-ferroportin axis is present and operational in PAECs. Modulation of this axis shows distinct differences in responses seen between PAECS and PASMCs. Stimulation of this axis in PAECS with hepcidin may well institute proliferative and migratory responses in PASMCs of relevance to pathogenesis of PAH offering a potential therapeutic target.

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Mitochondrial dysfunction in pulmonary arterial hypertension

Cited by 9 publications

References 168 publications

Pulmonary hypertension and insulin resistance: a mechanistic overview

Pulmonary hypertension and insulin resistance: a mechanistic overview

Research Progress on Chinese Medicine Regulation of Mitochondrial Damage for Intervention in Respiratory System Diseases

The hepcidin-ferroportin axis influences mitochondrial function, proliferation, and migration in pulmonary artery endothelial and smooth muscle cells

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