Contribution of STIM-Activated TRPC-ORAI Channels in Pulmonary
Hypertension Induced by Chronic Sustained and Intermittent Hypoxia

Castillo-Galán, Sebastián; Arenas, German A.; Iturriaga, Rodrigo

doi:10.2174/1570161120666220321141805

Cited by 6 publications

(1 citation statement)

References 132 publications

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“…When right HF occurs, systemic venous return is blocked, and fluid leakage in the chest increases, which leads to the occurrence of pleural effusion. This finding was consistent with the results of our study ( 16 ). OSAS is highly prevalent in patients with both HF with reduced ejection fraction and HF with preserved ejection fraction, and may contribute to the development of HF, which may reflect an important modifiable risk factor for patients with HF.…”

Section: Discussionsupporting

confidence: 94%

Serum levels of carbohydrate antigen 125 in patients with heart failure and obstructive sleep apnea syndrome: a retrospective analysis

Ge,

Song,

et al. 2023

Cardiovasc Diagn Ther

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Background Obstructive sleep apnea syndrome (OSAS) combined with heart failure (HF) has become a serious disease that threatens human health. Therapeutic interventions targeting OSAS have been shown to improve outcomes in patients with HF, so the identification of severe OSAS in HF is critical. Carbohydrate antigen 125 (CA125) is associated with inflammation and volume overload. The levels of CA125 are elevated in the serum of patients with HF and might be further elevated in patients with HF and OSAS. The aim of this study was to measure CA125 levels in patients with HF with and without OSAS and to analyze affecting factors. Methods In this single-center retrospective cohort study, a total of 95 patients diagnosed with HF hospitalized in Zhongda Hospital from April 2021 to April 2022 were recruited, including 55 patients with OSAS and 40 patients without OSAS. Participants with a history of central sleep apnea syndrome, severe chronic obstructive pulmonary disease, tumors, severe infection, or who were pregnant were excluded. The histories of the participants were recorded, and laboratory examinations were performed. Binary logistic regression analysis was performed to determine the relationship between serum CA125 levels and OSAS in patients with HF. Results The serum CA125 levels were higher in the HF + OSAS group than in the HF group (29.60 vs. 9.68 U/mL, P<0.001). According to the univariate analysis, CA125 (>35 U/mL) was significantly related to pleural effusion, acute HF, apnea-hypopnea index (AHI), left ventricular ejection fraction (LVEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Finally, the AHI demonstrated statistical significance in multiple analyses (OR 1.070, 95% CI: 1.019–1.124, P=0.006). Spearman rank correlation coefficient analysis showed that CA125 was positively correlated with AHI, and Ln(CA125) (Ln is the natural logarithm based on e) gradually increased with increasing AHI (r=0.551, P<0.0001). Conclusions The levels of CA125 were further increased in patients with HF and OSAS, and CA125 (>35 U/mL) was positively correlated with AHI. As a biomarker associated with inflammation and congestion, serum CA125 may have certain value in the diagnosis of patients with HF combined with OSAS.

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Section: Discussionsupporting

confidence: 94%

Serum levels of carbohydrate antigen 125 in patients with heart failure and obstructive sleep apnea syndrome: a retrospective analysis

Ge,

Song,

et al. 2023

Cardiovasc Diagn Ther

View full text Add to dashboard Cite

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Unraveling the pathogenesis of viral-induced pulmonary arterial hypertension: Possible new therapeutic avenues with mesenchymal stromal cells and their derivatives.

Castillo-Galán,

Parra,

Cuenca

2025

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Contribution of transient receptor potential canonical channels in human and experimental pulmonary arterial hypertension

Masson,

Saint-Martin Willer,

Dutheil

et al. 2023

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pulmonary arterial hypertension (PAH) is due to progressive distal pulmonary artery (PA) obstruction leading to right ventricular hypertrophy and failure. Exacerbated store-operated Ca2+ entry (SOCE) contributes to PAH pathogenesis, mediating human PA smooth muscle cells (hPASMCs) abnormalities. The transient receptor potential canonical channels (TRPC family) are Ca2+-permeable channels contributing to SOCE in different cell types, including PASMCs. However, the properties, signaling pathways, and contribution to Ca2+ signaling of each TRPC isoform are unclear in human PAH. We studied in vitro the impact of TRPC knockdown on control and PAH-hPASMCs function. In vivo, we analyzed the consequences of pharmacological TRPC inhibition using the experimental model of pulmonary hypertension (PH) induced by monocrotaline (MCT)-exposure. Compared to control-hPASMCs cells, in PAH-hPASMCs, we found a decreased TRPC4 expression, overexpression of TRPC3 and TRPC6, and unchanged TRPC1 expression. Using the siRNA strategy, we found that the knockdown of TRPC1-C3-C4-C6 reduced the SOCE and the proliferation rate of PAH-hPASMCs. Only TRPC1 knockdown decreased the migration capacity of PAH-hPASMCs. After PAH-hPASMCs exposure to the apoptosis inducer staurosporine, TRPC1-C3-C4-C6 knockdown increased the percentage of apoptotic cells, suggesting that these channels promote apoptosis resistance. Only TRPC3 function contributed to exacerbated calcineurin activity. In the MCT-PH rats' model, only TRPC3 protein expression was increased in lungs compared to control rats, and in vivo "curative" administration of a TRPC3 inhibitor attenuated PH development in rats. These results suggest that TRPC channels contribute to PAH-hPASMCs dysfunctions, including SOCE, proliferation, migration, apoptosis resistance, and could be considered as therapeutic targets in PAH.

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Contribution of STIM-Activated TRPC-ORAI Channels in Pulmonary Hypertension Induced by Chronic Sustained and Intermittent Hypoxia

Cited by 6 publications

References 132 publications

Serum levels of carbohydrate antigen 125 in patients with heart failure and obstructive sleep apnea syndrome: a retrospective analysis

Serum levels of carbohydrate antigen 125 in patients with heart failure and obstructive sleep apnea syndrome: a retrospective analysis

Unraveling the pathogenesis of viral-induced pulmonary arterial hypertension: Possible new therapeutic avenues with mesenchymal stromal cells and their derivatives.

Contribution of transient receptor potential canonical channels in human and experimental pulmonary arterial hypertension

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