Role of thrombin in the pathogenesis of atherosclerosis

Jaberi, Najmeh; Soleimani, Atena; Pashirzad, Mehran; Abdeahad, Hosein; Mohammadi, Fariba; Khoshakhlagh, Mahdieh; Khazaei, Majid; Rezayi, Majid; Hassanian, Seyed Mahdi

doi:10.1002/jcb.27771

Cited by 41 publications

(33 citation statements)

References 79 publications

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“…In fact, Alcalase has been previously reported to be the most effective protease to yield ACE-inhibitory peptides [ 36 , 37 ]. In addition, thrombin, which exerts the formation of blood clots, pro-inflammatory effects by stimulating the production of pro-inflammatory cytokines, and the onset of atherosclerosis [ 38 ] was determined in order to evaluate the thrombin-inhibitory activity of WGPHs ( Figure 2 B). WGPC (WGPH0A) inhibited 18.5% of thrombin activity.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Anti-Inflammatory and Atheroprotective Properties of Wheat Gluten Protein Hydrolysates in Primary Human Monocytes

Paz

Rodríguez-Martín

Villanueva

et al. 2020

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Bioactive protein hydrolysates have been identified in several sources as possible agents in the prevention and treatment of many diseases. A wheat gluten (WG) concentrate was hydrolyzed by Alcalase under specific conditions. The resulting hydrolysates were evaluated by in vitro cell-free experiments leading to the identification of one bioactive WG protein hydrolysate (WGPH), which was used at 50 and 100 μg/mL on primary human monocytes. Reactive oxygen species (ROS) and nitrite levels and RT-qPCR and ELISA techniques were used to analyze the functional activity of WGPH. Our results showed that WGPH hydrolyzed in 45 min (WGPH45A) down-regulated gene expression of Interleukin (IL)-1β, IL-6, IL-17, and Interferon gamma (IFNγ) and reduced cytokine release in lipopolysaccharide (LPS)-stimulated monocytes. In addition, WGPH45A down-regulated gene-related to atherosclerotic onset. Our results suggest that WGPH45A has a potent anti-inflammatory and atheroprotective properties, reducing the expression of gene-related inflammation and atherosclerosis that could be instrumental in maintaining cardiovascular homeostasis.

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Section: Resultsmentioning

confidence: 99%

Evaluation of Anti-Inflammatory and Atheroprotective Properties of Wheat Gluten Protein Hydrolysates in Primary Human Monocytes

Paz

Rodríguez-Martín

Villanueva

et al. 2020

Foods

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“…Given thrombin's effect on endothelial cells, it is not surprising that thrombin has been implicated in the pathogenesis of atherosclerosis. Thrombin has been widely studied for its role in the pathology of atherosclerosis, a progressive and chronic inflammatory vascular disorder (Kalz et al, 2014;Jaberi et al, 2019). A role for thrombin in the development of atherosclerosis is suggested by the observation that elevated levels of thrombin and the thrombin receptor PAR are found around atherosclerotic plaques, and that thrombin formation is correlated with disease severity in coronary atherosclerosis (Borissoff et al, 2012).…”

Section: Thrombin Contributes To the Development Of Alzheimer's Risk mentioning

confidence: 99%

Thrombin, a Mediator of Coagulation, Inflammation, and Neurotoxicity at the Neurovascular Interface: Implications for Alzheimer’s Disease

2020

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The societal burden of Alzheimer's disease (AD) is staggering, with current estimates suggesting that 50 million people worldwide have AD. Identification of new therapeutic targets is a critical barrier to the development of disease-modifying therapies. A large body of data implicates vascular pathology and cardiovascular risk factors in the development of AD, indicating that there are likely shared pathological mediators. Inflammation plays a role in both cardiovascular disease and AD, and recent evidence has implicated elements of the coagulation system in the regulation of inflammation. In particular, the multifunctional serine protease thrombin has been found to act as a mediator of vascular dysfunction and inflammation in both the periphery and the central nervous system. In the periphery, thrombin contributes to the development of cardiovascular disease, including atherosclerosis and diabetes, by inducing endothelial dysfunction and related inflammation. In the brain, thrombin has been found to act on endothelial cells of the blood brain barrier, microglia, astrocytes, and neurons in a manner that promotes vascular dysfunction, inflammation, and neurodegeneration. Thrombin is elevated in the AD brain, and thrombin signaling has been linked to both tau and amyloid beta, pathological hallmarks of the disease. In AD mouse models, inhibiting thrombin preserves cognition and endothelial function and reduces neuroinflammation. Evidence linking atrial fibrillation with AD and dementia indicates that anticoagulant therapy may reduce the risk of dementia, with targeting thrombin shown to be particularly effective. It is time for "outside-the-box" thinking about how vascular risk factors, such as atherosclerosis and diabetes, as well as the coagulation and inflammatory pathways interact to promote increased AD risk. In this review, we present evidence that thrombin is a convergence point for AD risk factors and as such that thrombin-based therapeutics could target multiple points of AD pathology, including neurodegeneration, vascular activation, and neuroinflammation. The urgent need for disease-modifying drugs in AD demands new thinking about disease pathogenesis and an exploration of novel drug targets, we propose that thrombin inhibition is an innovative tactic in the therapeutic battle against this devastating disease.

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Section: Introductionmentioning

confidence: 99%

“…Thrombin is another important mediator of platelet activation [10]. Thrombin is a serine protease that participates in the coagulation cascade, activating factors V, VIII, XI, and XII, converting fibrinogen to fibrin, and activating other cell types [10,11]. Both PAF and thrombin are produced during coagulation and inflammation and play a crucial role in platelet activation and thrombus formation via G protein-coupled receptors [12].…”

Section: Introductionmentioning

confidence: 99%

Total, Neutral, and Polar Lipids of Brewing Ingredients, By-Products and Beer: Evaluation of Antithrombotic Activities

Lordan

O’Keeffe

Τσούπρας

2019

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The in vitro antithrombotic properties of polar lipid constituents of malted grain (MG), pelleted hops (PH), brewer’s spent grain (BSG), spent hops (SH), wort, and bottled beer from the same production line were assessed in human platelets. The total lipids (TL) were extracted according to the Bligh and Dyer method and further separated into the total neutral lipids (TNL) and total polar lipids (TPL) extracts by counter-current distribution. The TL, TNL, and TPL extracts of all samples were assessed for their ability to inhibit platelet-activating factor (PAF) and thrombin-induced human platelet aggregation. The raw materials, by-products, wort, and beer lipid extracts all exhibited antithrombotic properties against PAF and thrombin. However, the beer TPL exhibited the lowest IC50 values against PAF-induced (7.8 ± 3.9 µg) and thrombin-induced (4.3 ± 3.0 µg) platelet aggregation indicating that these polar lipids were the most antithrombotic. The lipid extracts tended to be more bioactive against the thrombin pathway. The fatty acid content of all the TPL extracts were assessed using GC-MS. The fatty acid composition of the most bioactive TPL extracts, the wort and the beer, shared similar fatty acid profiles. Indeed, it was noted that fermentation seems to play a role in increasing the antithrombotic properties of polar lipids against PAF and thrombin by moderately altering the polar lipid fatty acid composition. Furthermore, the use of brewing by-products as a source of functional cardioprotective lipids warrants further investigation and valorisation.

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Role of thrombin in the pathogenesis of atherosclerosis

Cited by 41 publications

References 79 publications

Evaluation of Anti-Inflammatory and Atheroprotective Properties of Wheat Gluten Protein Hydrolysates in Primary Human Monocytes

Evaluation of Anti-Inflammatory and Atheroprotective Properties of Wheat Gluten Protein Hydrolysates in Primary Human Monocytes

Thrombin, a Mediator of Coagulation, Inflammation, and Neurotoxicity at the Neurovascular Interface: Implications for Alzheimer’s Disease

Total, Neutral, and Polar Lipids of Brewing Ingredients, By-Products and Beer: Evaluation of Antithrombotic Activities

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