Plasminogen activator inhibitor links obesity and thrombotic cerebrovascular diseases: The roles of PAI-1 and obesity on stroke

Chen, Rui; Yan, Jinchuan; Liu, Peijing; Wang, Zhongqun; Wang, Cuiping

doi:10.1007/s11011-017-0007-3

Cited by 44 publications

(33 citation statements)

References 64 publications

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“…Ours is the first generation in the 200,000-year history of Homo sapiens where more members of our species are overweight and obese than underweight (Di Cesare et al, 2016). This sudden rise in global obesity prevalence from 105 million individuals in 1975 to 641 million in 2014 (Di Cesare et al, 2016) has coincided with a rise in a plethora of obesity related pathologies including cardiovascular disease (Florido et al, 2017), diabetes mellitus (Al-Goblan, Al-Alfi, & Khan, 2014), cancer (Zheng et al, 2017), stroke (R. Chen, Yan, Liu, Wang, & Wang, 2017), vascular dementia (Ilenia, Daniele, Michele, Enea, & Tayebati, 2017), and Alzheimer's disease (Ilenia et al, 2017). Although obesity is most commonly defined as a body mass index or BMI (body mass divided by the square of the body height) of over 30 kg/m 2 , it is fundamentally characterized by an aberrant and excessive accumulation of adipose tissue due to adipocyte hyperplasia and hypertrophy (Muir et al, 2016).…”

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confidence: 99%

Dehydroleucodine inhibits mitotic clonal expansion during adipogenesis through cell cycle arrest

Abood

Veisaga

López

et al. 2018

Phytotherapy Research

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Aberrant levels of preadipocyte differentiation, triggered by adipocyte hyperplasia and hypertrophy, results in the obesogenic phenotype. Obesity is a risk factor for several metabolic disorders. In this paper, dehydroleucodine inhibited the accumulation of lipid droplets and decreased the elevations of triglycerides, and this inhibitory effect occurred during the early stage of adipogenesis. Thus, not only did dehydroleucodine downregulate the expression of C/EBPα and PPARγ, it also strongly blocked the expression of C/EBPβ, an early stage biomarker of early adipogenesis, in a concentration-dependent manner. The proliferation of preadipocytes was dramatically suppressed when dehydroleucodine was added to the medium as early as 24 hr. These results indicate that dehydroleucodine may specifically affect mitotic clonal expansion to inhibit preadipocyte differentiation. Dehydroleucodine arrested the cell cycle at the G /G phase, increased p27 and decreased both cyclins A and D and their partners (e.g., CDK2 and CDK4). Additionally, dehydroleucodine decreased phosphorylation of Erk1/2 and Akt. Furthermore, dehydroleucodine downregulated expression of histone demethylase JMJD2B as well as repressed the expression of histone methyltransferase MLL4, which in turn diminished the expression of C/EBPβ and PPARγ, respectively. Collectively, our results indicate that dehydroleucodine inhibits preadipocyte differentiation by blocking mitotic clonal expansion via cell cycle arrest, which may be mediated by regulation of selective histone methylation/demethylation in transcription activation during the early step of adipogenesis.

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confidence: 99%

Dehydroleucodine inhibits mitotic clonal expansion during adipogenesis through cell cycle arrest

Abood

Veisaga

López

et al. 2018

Phytotherapy Research

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“…The reasons for the discrepancy between the effects of CK and KM on TNF-α induced PAI-1 production in EA.hy926 cells and in mice were not clear. It is reported that LPS stimulates TNF-α production from adipocytes and macrophages and produed TNF-α induces PAI-1expression in endothelial cells [36] [37]. Concentrated Kurozu may decrease plasma PAI-1 level (or PAI-1 production) through only inhibiting TNF-α production of adipocytes and macrophages stimulated by LPS.…”

Section: Discussionmentioning

confidence: 99%

Effects of Fermented Rice Vinegar Kurozu and Its Sediment on Inflammation-Induced Plasminogen Activator Inhibitor 1 (PAI-1) Increase

Ohkura¹,

Kihara-Negishi²,

Fujii³

et al. 2018

FNS

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Kurozu is a traditional black rice vinegar in Japan. Kurozu-moromi is the solid sediment that arises during the production of Kurozu. Kurozu is thought to have blood thinning and antithrombotic activities but a specific effect has not been proven. Plasma plasminogen activator inhibitor 1 (PAI-1) inhibits fibrinolysis and when elevated, it is a risk factor for the development of thrombotic diseases. Here, we examined the effects of a diet containing Kurozu and Kurozu-moromi on LPS (lipopolysaccharide)-induced increases in plasma PAI-1 levels in mice and on TNF-α (tumor necrosis factor α) increased PAI-1 production in the medium of a cultured endothelial cell line. Mice were fed with a diet containing 0.25% (w/w) concentrated Kurozu or 0.5% (w/w) Kurozu-moromi for four weeks, and then subcutaneously injected with 0.015 mg/kg of LPS in saline and sacrificed three hours later. Orally administered concentrated Kurozu and Kurozu-moromi significantly suppressed the LPS-induced increase in PAI-1 antigen and its activity in mouse plasma. The ethanol extract of Kurozu-moromi inhibited TNF-α induced increases of PAI-1 in the culture medium of the EA.hy926 endothelial cell line. The present findings showed that Kurozu and Kurozu-moromi contain natural products that decrease thrombotic tendencies by decreasing PAI-1 production in inflammatory states and have potential as antithrombotic foodstuffs.

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“…PAI-1 deposits in the extracellular matrix facilitate the formation of atherosclerotic plaques, thicken the vascular basement membrane and stiffen the vascular walls, thus promoting the onset and development of vasculopathy and therefore atherosclerosis (35)(36)(37). PAI-1 is considered to be closely associated with vascular disease (38); therefore, it is important to determine the regulatory mechanism of action of PAI-1. The present study identified the relevant factors in AMI in the peripheral blood.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑30b protects myocardial cell function in patients with acute myocardial ischemia by targeting plasminogen activator inhibitor‑1

Chen

2018

Exp Ther Med

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The aim of the present study was to determine the expression of plasminogen activator inhibitor-1 (PAI-1) and microRNA (miR)-30b in the blood of patients with acute myocardial ischemia (AMI) and in the blood and myocardial tissue of mice with AMI. In addition, the present study aimed to identify the mechanism of action of miR-30b in AMI. A total of 36 patients with AMI were included in the present study and 28 healthy subjects were included as a control. Peripheral blood was collected from all subjects. For animal experiments, mice in the AMI group received an intraperitoneal injection of pituitrin (20 U/kg), whereas mice in the negative control group received an intraperitoneal injection of the same volume of saline. Blood and myocardial tissue was collected from all mice for analysis. Reverse transcription-quantitative polymerase chain reaction was performed to determine the expression of PAI-1 mRNA and miR-30b in the serum and myocardial tissue. An enzyme-linked immunosorbent assay was performed to measure the expression of PAI-1 protein in the serum of humans and mice, whereas western blotting was performed to determine the expression of PAI-1 protein in mouse myocardial tissue. Catalase, glutathione peroxidase and superoxide dismutase activity was measured using an automatic biochemical analyzer. A dual luciferase assay was performed to identify the interactions between PAI-1 mRNA and miR-30b. The results indicated that patients with AMI have higher PAI-1 levels and lower miR-30b expression in the peripheral blood compared with healthy subjects. AMI damaged the myocardium tissue of mice and reduced catalase, glutathione peroxidase and superoxide dismutase activity. Mice that have undergone AMI exhibit increased PAI-1 levels but decreased miR-30b expression in the peripheral blood and myocardial tissues. It was also demonstrated that miR-30b is able to bind to the 3'-untranslated region of PAI-1 mRNA to regulate its expression. The present study demonstrates that patients with AMI exhibit decreased miR-30b expression and elevated PAI-1 expression in the peripheral blood. miR-30b may therefore inhibit the damage to myocardial cells that occurs following AMI and protect myocardial cell function by targeting PAI-1 expression.

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Plasminogen activator inhibitor links obesity and thrombotic cerebrovascular diseases: The roles of PAI-1 and obesity on stroke

Cited by 44 publications

References 64 publications

Dehydroleucodine inhibits mitotic clonal expansion during adipogenesis through cell cycle arrest

Dehydroleucodine inhibits mitotic clonal expansion during adipogenesis through cell cycle arrest

Effects of Fermented Rice Vinegar Kurozu and Its Sediment on Inflammation-Induced Plasminogen Activator Inhibitor 1 (PAI-1) Increase

MicroRNA‑30b protects myocardial cell function in patients with acute myocardial ischemia by targeting plasminogen activator inhibitor‑1

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