scholarly journals C-Reactive Protein and Complement Are Important Mediators of Tissue Damage in Acute Myocardial Infarction

1999 ◽  
Vol 190 (12) ◽  
pp. 1733-1740 ◽  
Author(s):  
M. Griselli ◽  
J. Herbert ◽  
W.L. Hutchinson ◽  
K.M. Taylor ◽  
M. Sohail ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Myocardial Injury ◽  
Peak Plasma ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Coronary Ligation

Myocardial infarction in humans provokes an acute phase response, and C-reactive protein (CRP), the classical acute phase plasma protein, is deposited together with complement within the infarct. The peak plasma CRP value is strongly associated with postinfarct morbidity and mortality. Human CRP binds to damaged cells and activates complement, but rat CRP does not activate complement. Here we show that injection of human CRP into rats after ligation of the coronary artery reproducibly enhanced infarct size by ∼40%. In vivo complement depletion, produced by cobra venom factor, completely abrogated this effect. Complement depletion also markedly reduced infarct size, even when initiated up to 2 h after coronary ligation. These observations demonstrate that human CRP and complement activation are major mediators of ischemic myocardial injury and identify them as therapeutic targets in coronary heart disease.

The Effect of Factor Xa/Phospholipid Infusion on the Acute Phase Response in Baboons

1997 ◽  
Vol 77 (02) ◽  
pp. 308-311 ◽  
Author(s):  
Egbert K O Kruithof ◽  
Diane Agay ◽  
Jean Claude Mestries ◽  
Marie-Paule Gascon ◽  
Arnaud Ythier
Keyword(s):  
Acute Phase ◽  
Interleukin 6 ◽  
Acute Phase Response ◽  
Tissue Injury ◽  
Peak Plasma ◽  
Factor Xa ◽  
Phase Response ◽  
C Reactive Protein ◽  
Reactive Protein

SummaryDisseminated intravascular coagulation (DIC) is a frequent complication of septicemia or tissue injury and may be accompanied by elevations of interleukin-6, a mediator of the acute phase response. It is not known whether thrombin or fibrin deposition may directly induce an acute phase response. To study this, we employed a baboon model of in vivo thrombin generation, induced by the administration of purified bovine Factor Xa and phospholipid vesicles. Two Xa/phospholipid dosages were used, a low dosage (2 animals) leading to a rapid 49% decrease in fibrinogen and a high dosage (two injections at 5h interval; 3 animals) leading to complete fibrinogen depletion. Thereafter, fibrinogen levels increased in both treatment groups, reached a maximum of 2.52 ± 0.23 g/1 (mean ± SE, n = 5; p <0.01 with respect to basal levels) at day 2, and returned to normal by day seven. In five control (injection of 0.15% NaCl) baboons no significant changes of fibrinogen were observed (maximal values: 1.88 ± 0.12 g/1). Serum concentrations of C-reactive protein, an acute phase protein, increased from 3.7 ± 0.4 mg/1 to a maximum of 33.0 ± 7.3 at day one, which was five-fold higher (p <0.01) than in control animals at day one (6.2 ± 0.5 mg/1). Transient increases were observed within 6 h for interleukin-6 from basal values of 6.2 ± 1.7 ng/1 to peak plasma levels of 42.9 ±21.4 ng/1, a value threefold higher (p = 0.07) than in control animals (14.8 ± 4.0 ng/1).The preliminary results of this observational study suggest that factor Xa/phospholipid infusion is followed by an acute phase response, leading after one day to significant increases of fibrinogen and of C-reactive protein.

Acute phase response after myocardial infarction: Correlation between serum levels of cytokines and C-reactive protein

1990 ◽  
Vol 68 (21) ◽  
pp. 1083-1083 ◽  
Author(s):  
H. Tilg ◽  
J. Mair ◽  
M. Herold ◽  
W. E. Aulitzky ◽  
P. Lechleitner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Serum Levels ◽  
Phase Response ◽  
C Reactive Protein ◽  
Reactive Protein

Histone-Induced Lung Injury and Coagulation Activation Are Reduced By C-Reactive Protein In The Acute Phase Response

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 457-457
Author(s):  
Simon Timothy Abrams ◽  
Nan Zhang ◽  
Guozheng Wang ◽  
Cheng-Hock Toh
Keyword(s):  
Endothelial Cell ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Lethal Dose ◽  
Lung Edema ◽  
Trauma Patients ◽  
C Reactive Protein ◽  
Coagulation Activation ◽  
Reactive Protein

Whilst histones are essential building blocks within cells in forming the basis of chromatin, their extracellular effects can be extremely toxic. We have shown in in vivo models with translational relevance to patients with severe trauma that circulating histones increase mortality through acute lung injury with multifocal alveolar hemorrhage, thrombi formation and severe lung edema. from patients within 4 hours of trauma exhibited histone-specific endothelial cell toxicity when histone levels reached 50 µg/ml. threshold was associated with increased interleukin (IL)-6 levels (r=0.55, p < 0.01) and thrombin-antithrombin (TAT) levels. However, serum from trauma patients at timepoints beyond 6 hours no longer exhibited histone-specific toxicity despite elevated histone levels. These samples were found to have increasing levels of C reactive protein (CRP), which were low until 4-6 hours post trauma. To examine if CRP could be neutralising the toxicity of circulating histones, in vitro culture systems demonstrate that CRP release is linked to extracellular histones as histones induce leucocytes to release pre-synthesized IL-6, which in turn induces the release of CRP by hepatocytes. a biosensor and gel overlay assays, CRP interacts with all individual histones and forms. Functionally, CRP (100 µg/ml) significantly reduces histone-induced endothelial cell damage, permeability increase and platelet aggregation by ∼50% (p < 0.05), which is confirmed in vivo as CRP (10 mg/kg) inhibits endothelial damage [reduced circulating sTM by 1 fold (p < 0.05)], vascular permeability [reduced Lung wet/dry weight ratio to control levels (p < 0.05)], coagulation activation [reduced circulating TAT by 1 fold (p < 0.05)] and thrombocytopenia [increased platelet/HCT ratio by 2 folds (p < 0.05)]. Histological examination showed that CRP-infusion reduced lung edema, hemorrhage and thrombosis in mice challenged by a lethal dose of histones (75 mg/kg) to rescue these mice., induction of the acute phase response using casein reduced histone-induced pathological changes and protected mice challenged with a lethal dose of histones. trauma patients, CRP–histone complexes could be detected and was responsible for the loss of histone-specific cytotoxicity as addition of exogenous CRP to clinical samples with high histone but low CRP levels abolished the cytotoxic effects. The histone-specific manner was similar to the effect of incubating the patient samples with an anti-histone antibody. In conclusion, elevation in circulating histones following extensive cell death results in an acute phase reaction that involves CRP in neutralising further histone-induced cytotoxicity., this is a new specific role described for human CRP amidst its properties in generic host defence. Clinically, this CRP response lags behind the histone surge in patients and a time-critical period therefore exists for potential clinical interventions using anti-histone reagents. Disclosures: No relevant conflicts of interest to declare.

Acute-Phase Plasma PCSK9 Levels and Recurrent Cardiovascular Events in a Chinese Acute Myocardial Infarction Cohort

Cardiology ◽  
2018 ◽  
Vol 141 (2) ◽  
pp. 88-97 ◽  
Author(s):  
Yan Gao ◽  
Yan Qiu ◽  
Jihua Wu ◽  
Wei Diao ◽  
Haibo Zhang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Acute Phase ◽  
Recurrent Events ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
Female Gender ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Increased Risk

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular (CV) disease. Whether plasma PCSK9 measured during the acute phase predicts recurrent CV events in patients with acute myocardial infarction (AMI) remains unresolved. Methods and Results: Plasma PCSK9 levels were measured in 1,646 patients with AMI from the China PEACE-Prospective AMI Study at the acute phase. Additionally, 248 patients were resampled and measured at 1 month post-AMI. Associations of acute-phase PCSK9 tertiles with clinical characteristics and recurrent CV events within 1 year were assessed. Female gender (OR 1.94, 95% CI 1.24–3.03), premature coronary heart disease (CHD; OR 2.12, 95% CI 1.37–3.26), higher high-sensitivity C-reactive protein (OR 1.67, 95% CI 1.44–1.95), and higher triglycerides (OR 1.46, 95% CI 1.03–2.09) were associated with higher baseline PCSK9. Plasma PCSK9 levels in the highest tertile (versus lowest) did not have an increased risk of 1-year recurrent CV events in the AMI cohort (HR 0.78, 95% CI 0.52–1.16) or any subgroup. There was also no association between percentage changes in PCSK9 over the first month and 1-year recurrent events, although there was a trend of differences between patients in the upper versus lower tertiles. Conclusion: Plasma PCSK9 levels measured during the acute phase were associated with high-sensitivity C-reactive protein, triglycerides, premature CHD, and gender in patients with AMI but did not predict recurrent CV events within 1 year. Dynamic changes in PCSK9 suggested a trend yet no significance value in predicting recurrent CV events.

The acute phase response and C-reactive protein

2020 ◽  
pp. 2199-2207
Author(s):  
Mark B. Pepys
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Serum Amyloid A ◽  
Acute Phase Proteins ◽  
Phase Response ◽  
Serum Amyloid ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Amyloid A ◽  
Serum Amyloid A Protein

The acute phase response—trauma, tissue necrosis, infection, inflammation, and malignant neoplasia induce a complex series of nonspecific systemic, physiological, and metabolic responses including fever, leucocytosis, catabolism of muscle proteins, greatly increased de novo synthesis and secretion of a number of ‘acute phase’ plasma proteins, and decreased synthesis of albumin, transthyretin, and high- and low-density lipoproteins. The altered plasma protein concentration profile is called the acute phase response. Acute phase proteins—these are mostly synthesized by hepatocytes, in which transcription is controlled by cytokines including interleukin 1, interleukin 6, and tumour necrosis factor. The circulating concentrations of complement proteins and clotting factors increase by up to 50 to 100%; some of the proteinase inhibitors and α‎1-acid glycoprotein can increase three- to fivefold; but C-reactive protein (CRP) and serum amyloid A protein (an apolipoprotein of high-density lipoprotein particles) are unique in that their concentrations can change by more than 1000-fold. C-reactive protein—this consists of five identical, nonglycosylated, noncovalently associated polypeptide subunits. It binds to autologous and extrinsic materials which contain phosphocholine, including bacteria and their products. Ligand-bound CRP activates the classical complement pathway and triggers the inflammatory and opsonizing activities of the complement system, thereby contributing to innate host resistance to pneumococci and probably to recognition and safe ‘scavenging’ of cellular debris. Clinical features—(1) determination of CRP in serum or plasma is the most useful marker of the acute phase response in most inflammatory and tissue damaging conditions. (2) Acute phase proteins may be harmful in some circumstances. Sustained increased production of serum amyloid A protein can lead to the deposition of AA-type, reactive systemic amyloid.

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