Effects of α1-acid glycoprotein on hemostasis in experimental septic peritonitis

Осиков, М. В.; Makarov, E. V.; Кривохижина, Л. В.

doi:10.1007/s10517-007-0283-8

Cited by 11 publications

(10 citation statements)

References 3 publications

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“…In an experimental model of peritonitis in rats, high doses of a-1-AGP normalized platelet aggregation, blood clotting parameters and antithrombin activity. 57 Increased amounts of a-1-AGP inhibit platelet aggregation induced by ADP and adrenaline.…”

Section: Discussionmentioning

confidence: 99%

A meta-analysis of genome-wide association studies identifies ORM1 as a novel gene controlling thrombin generation potential

Rocañín-Arjó

Cohen

Carcaillon

et al. 2014

Blood

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Key Points• Genetic variations at the ORM1 locus and concentrations of the encoded protein associate with thrombin generation.• These findings may guide the development of novel antithrombotic treatments.Thrombin, the major enzyme of the hemostatic system, is involved in biological processes associated with several human diseases. The capacity of a given individual to generate thrombin, called the thrombin generation potential (TGP), can be robustly measured in plasma and was shown to associate with thrombotic disorders. To investigate the genetic architecture underlying the interindividual TGP variability, we conducted a genome-wide association study in 2 discovery samples (N 5 1967) phenotyped for 3 TGP biomarkers, the endogenous thrombin potential, the peak height, and the lag time, and replicated the main findings in 2 independent studies (N 5 1254). We identified the ORM1 gene, coding for orosomucoid, as a novel locus associated with lag time variability, reflecting the initiation process of thrombin generation with a combined P value of P 5 7.1 3 10 215 for the lead single nucleotide polymorphism (SNP) (rs150611042). This SNP was also observed to associate with ORM1 expression in monocytes (P 5 8.7 3 10 210 ) and macrophages (P 5 3.2 3 10 23 ). In vitro functional experiments further demonstrated that supplementing normal plasma with increasing orosomucoid concentrations was associated with impaired thrombin generation. These results pave the way for novel mechanistic pathways and therapeutic perspectives in the etiology of thrombin-related disorders. (Blood. 2014;123(5):777-785)

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Section: Discussionmentioning

confidence: 99%

A meta-analysis of genome-wide association studies identifies ORM1 as a novel gene controlling thrombin generation potential

Rocañín-Arjó

Cohen

Carcaillon

et al. 2014

Blood

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“…148 An acute septicemia model resulted in elevated CP levels, and the provision of exogenous AGP was observed to decrease the severity of the inflammatory response. 149 Trauma related to surgery for castration or oophorohysterectomy induced similar levels. 148 Rabbit APP studies have concentrated on experimental inflammatory stimuli.…”

Section: A Rodents and Rabbitsmentioning

confidence: 96%

Acute Phase Proteins in Animals

Cray

2012

Progress in Molecular Biology and Translational Science

507

701

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Acute phase proteins (APP) were first identified in the early 1900s as early reactants to infectious disease. They are now understood to be an integral part of the acute phase response (APR) which is the cornerstone of innate immunity. APP have been shown to be valuable biomarkers as increases can occur with inflammation, infection, neoplasia, stress, and trauma. All animals--from fish to mammals--have demonstrable APP, but the type of major APP differs by species. While the primary application of these proteins in a clinical setting is prognostication, studies in animals have demonstrated relevance to diagnosis and detection and monitoring for subclinical disease. APP have been well documented in laboratory, companion, and large animals. With the advent of standardized and automated assays, these biomarkers are available for use in all fields of veterinary medicine as well as basic and clinical research.

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“…The abnormal renal tissue is probably characterized by a functional defi ciency of AGP. Protective activity of AGP may be also related to the actoxifi cation and antioxidant properties [2].…”

Section: Resultsmentioning

confidence: 99%

Role of Orosomucoid in the Regulation of Plasma Proteolytic Systems during Experimental Renal Failure

Осиков

2009

Bull Exp Biol Med

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Activity of plasma proteolytic systems was studied in outbred albino rats with acute renal failure. The possibility of treating this disorder with acute phase protein alpha-1-acid glycoprotein was evaluated. Acute renal failure was induced by single subcutaneous injection of mercury chloride (II). The parameters were evaluated on day 5 postinjection. alpha-1-Acid glycoprotein in a dose of 150 mg/kg was administered 3 times. Acute renal failure was accompanied by activation of the complement system and fibrin formation (with factors for the intrinsic and common pathways of blood coagulation) and inhibition of the fibrinolytic system and antithrombin activity. Treatment with glycoprotein was followed by partial recovery of fibrin formation and complement system. These changes were probably related to accumulation of glycoprotein in the renal tissue and in situ protective effect.

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Effects of α1-acid glycoprotein on hemostasis in experimental septic peritonitis

Cited by 11 publications

References 3 publications

A meta-analysis of genome-wide association studies identifies ORM1 as a novel gene controlling thrombin generation potential

A meta-analysis of genome-wide association studies identifies ORM1 as a novel gene controlling thrombin generation potential

Acute Phase Proteins in Animals

Role of Orosomucoid in the Regulation of Plasma Proteolytic Systems during Experimental Renal Failure

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