Plasminogen activator inhibitor-1 is elevated in patients with COPD independent of metabolic and cardiovascular function

Waschki, Benjamin; Watz, Henrik; Holz, Olaf; Magnussen, H; Olejnicka, Beata; Welte, Tobias; Rabe, Klaus F.; Janciauskiene, Sabina

doi:10.2147/copd.s128689

Cited by 30 publications

(33 citation statements)

References 38 publications

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“…Our findings provide convincing evidence that serum concentrations of adiponectin were higher in COPD patients than in healthy controls. This result of the pooled analysis is in accordance with most findings of previous studies [15][16][17]19,20,[23][24][25]27]. Serum adiponectin levels correlated inversely with BMI in patients with COPD [20,22,23,27], which indicates that the adipose tissue may be an important influence factor to the serum adiponectin level in COPD.…”

Section: Discussionsupporting

confidence: 91%

“…Finally, 13 articles were included for this meta-analysis, containing 1131 COPD patients and 689 controls in total. The subjects of nine studies were stable COPD patients [15][16][17][18][19][20][21][22][23], three studies involved stable COPD patients and AECOPD patients [24][25][26], and one study involved mixed COPD patients [27]. In 12 studies [15][16][17][18][19][20][21][22][23][25][26][27], the control participants were matched for all the main confounders (BMI, age, gender) with the OSA patients.…”

Section: Study Inclusion and Characteristicsmentioning

confidence: 99%

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Association between serum adiponectin concentrations and chronic obstructive pulmonary disease: a meta-analysis

Lin

Jiang

et al. 2020

Bioscience Reports

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Background: Adiponectin has been implicated to play a role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Many studies have assessed serum adiponectin concentrations in COPD patients. However, results from different reports were not consistent. To assess the association of serum adiponectin concentrations and COPD, a meta-analysis was performed. Methods: PubMed, Embase, Web of Science and Cochrane Library were searched for eligible studies. Data were extracted, and then standard mean differences (SMDs) and 95% confidence intervals (CI) were calculated. Results: Thirteen studies involving a total of 1131 cases and 689 controls were included in this meta-analysis. Combined data indicated that the serum adiponectin levels were higher in COPD patients than those in controls (SMD: 1.09, 95% CI [0.73-1.45], P < 0.001). In the subgroup analyses by disease period, there were similar results in stable COPD patients (SMD: 0.77, 95% CI [0.47-1.07], p <0.001; I 2 = 83.9%, P < 0.001), AECOPD patients (SMD: 2.51, 95% CI [0.71-4.30], P = 0.006; I 2 = 95.2%, P < 0.001) and mixed COPD patients (SMD: 1.21, 95% CI [0.67-1.75], P < 0.001). Furthermore, the serum adiponectin levels were higher in AECOPD patients than those in stable COPD patients (SMD: 1.06, 95% CI [0.13-1.99], P = 0.026). Conclusions: This meta-analysis indicates that patients with COPD have higher serum adiponectin concentration than healthy controls.

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Section: Discussionsupporting

confidence: 91%

Section: Study Inclusion and Characteristicsmentioning

confidence: 99%

Association between serum adiponectin concentrations and chronic obstructive pulmonary disease: a meta-analysis

Lin

Jiang

et al. 2020

Bioscience Reports

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“…In the current study, although the majority of stroke events among COPD patients were of the ischemic type, the association between COPD and the risk of hemorrhagic stroke was also robust. Levels of plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of fibrinolysis, were found to be higher in COPD patients and may contribute to thrombosis and ischemic stroke among these patients 37 . Plasminogen activators were found to be beneficial for patients with mild stroke 38 .…”

Section: Discussionmentioning

confidence: 99%

Stroke risk among patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis

Kim

Hwang

Lee

et al. 2018

Clinics

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Increased stroke risk among chronic obstructive pulmonary disease patients has not yet been established. In this study, we conducted a systematic review and meta-analysis to assess stroke risk among chronic obstructive pulmonary disease patients. PubMed, EMBASE, and the Cochrane Library were systematically searched from database inception until December 31, 2016 to identify longitudinal observational studies that investigated the association between chronic obstructive pulmonary disease and stroke. Stroke risk was quantified by overall and subgroup analyses, and a pooled hazard ratio was calculated. Study quality was evaluated using the Newcastle-Ottawa Scale. Publication bias was assessed using Begg’s rank correlation test. Eight studies met the inclusion criteria. In a random-effects model, significantly increased stroke risk was observed among chronic obstructive pulmonary disease patients (hazard ratio, 1.30; 95% confidence interval, 1.18-1.43). In subgroup analyses stratified by stroke subtype, study quality, and adjustment by socioeconomic status, the association between increased stroke risk and chronic obstructive pulmonary disease patients was robust. Statistically significant publication bias was not detected. In summary, chronic obstructive pulmonary disease was found to be associated with increased stroke risk. Additional prospective studies are required to elucidate the mechanisms underlying the increase in stroke risk and identify effective preventive interventions.

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“…Collectively, these results reveal that Adp might play an important role in regulating the fibrinolytic system. In addition, elevated PAI-1 levels may be involved in obesity, metabolic syndrome, diabetes mellitus, thrombosis, endometriosis, atherosclerosis, cancer, and multiple organ fibrosis [21][22][23][24]; we predicated that Adp may be utilized as a novel agent in the treatment of these human diseases. However, to assess the effects of Adp on fibrinolytic balance, theexpressionlevels of t-PA, u-PA, and u-PA receptor (u-PAR) need to be examined because fibrinolysis is determined by a balance of inhibitors and activators.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin Inhibits TNF-α-Activated PAI-1 Expression Via the cAMP-PKA-AMPK-NF-κB Axis in Human Umbilical Vein Endothelial Cells

Chen¹,

Zheng²,

Liu³

et al. 2017

Cell Physiol Biochem

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Background: Tumor necrosis factor (TNF)-α can upregulate the expression of plasminogen activator inhibitor (PAI)-1, an inhibitor of fibrinolysis. Adiponectin (Adp) antagonizes TNF-α by negatively regulating its expression in various tissues. In the present study, the ability of Adp to suppress TNF-α-induced PAI-1 upregulation and the underlying mechanisms were evaluated. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with TNF-α in the presence or absence of Adp, and PAI-1 mRNA and antigen expression, activated signaling pathways, and molecular mechanisms were analyzed by qRT-PCR and ELISA. Results: Adp decreased the TNF-α-induced upregulation of PAI-1 mRNA and protein expression and suppressed TNF-α-induced cAMP-PKA-AMPK inactivation. Adp also suppressed the TNF-α-induced NF-kB binding capability on the PAI-1 promoter. Moreover, these Adp-induced effects were further enhanced or prevented by treatment with the cAMP inhibitor Rp-cAMPs or activator forskolin, respectively. Conclusions: Our data suggest that Adp abrogates TNF-α-activated PAI-1 expression by activating cAMP-PKA-AMPK signaling to suppress NF-kB binding to the PAI-1 promoter in HUVECs. Given the antifibrotic effect of PAI-1 abrogation, Adp may be utilized as a novel agent in the treatment of fibrotic diseases.

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Plasminogen activator inhibitor-1 is elevated in patients with COPD independent of metabolic and cardiovascular function

Cited by 30 publications

References 38 publications

Association between serum adiponectin concentrations and chronic obstructive pulmonary disease: a meta-analysis

Association between serum adiponectin concentrations and chronic obstructive pulmonary disease: a meta-analysis

Stroke risk among patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis

Adiponectin Inhibits TNF-α-Activated PAI-1 Expression Via the cAMP-PKA-AMPK-NF-κB Axis in Human Umbilical Vein Endothelial Cells

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