CRP, a major culprit in complement-mediated tissue damage in acute myocardial infarction?

Nijmeijer, R.; Lagrand, Wim K.; Visser, Cees A.; Meijer, Chris J.L.M.; Niessen, Hans W.M.; Hack, C. Erik

doi:10.1016/s1567-5769(00)00044-8

Cited by 42 publications

(27 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…28) Moreover, it has also been suggested that CRP is not only a marker of inflammation, but also an active participant and amplifier in the process of AMI. 29) On the other hand, it has also been demonstrated that high CRP levels both on admission 6) and at peak 30) are associated with the occurrence of mild to severe HF (Killip class II to IV) during the hospitalization period in AMI patients, and there are also studies in which higher admission CRP levels were observed in AMI patients who developed CS during the pre-or postadmission period. 8,9) In general, these observations are in agreement with our results.…”

Section: Discussionmentioning

confidence: 99%

Admission Levels of C-Reactive Protein and Plasminogen Activator Inhibitor-1 in Patients With Acute Myocardial Infarction With and Without Cardiogenic Shock or Heart Failure on Admission

et al. 2009

View full text Add to dashboard Cite

SummaryScarce data exist on the relationship of C-reactive protein (CRP) or plasminogen activator inhibitor-1 (PAI-1) to the occurrence of heart failure (HF) or cardiogenic shock (CS) after acute myocardial infarction (AMI) and on the relationship between these biomarkers and mortality in CS patients. Thus, we compared high-sensitivity CRP and PAI-1 antigen plasma levels on admission among 3 age-and gender-matched AMI patients groups (consisting of 60 patients with CS, 60 with HF, and 60 without HF on admission), after determining that PAI-1 levels did not vary significantly diurnally in these groups by comparing the data among subgroups which were divided according to admission time within the groups. For CS patients, we also conducted regression analyses to examine the relations of these biomarkers to mortality. CRP levels both in CS (P < 0.001) and HF (P < 0.05) patients were significantly higher compared to those without HF, PAI-1 levels in CS patients were significantly higher compared to both those with (P < 0.05) and without HF (P < 0.01), and CRP and PAI-1 were independent predictors of in-hospital (Odds ratio [OR] = 6.12, 95% confidence intervals [95%CI] = 1.47-25.54 and OR = 5.92, 95%CI = 1.31-26.77, respectively) and 1-year mortality (OR = 5.53, 95%CI = 1.21-25.17 and OR = 5.48, 95%CI = 1.09-27.52, respectively) in CS patients. In conclusion, at admission, CRP is associated with the occurrence of CS and HF and PAI-1 is associated with the occurrence of CS after AMI, and they are of prognostic value in CS complicating AMI. (Int Heart J 2009; 50: 33-45)

show abstract

Section: Discussionmentioning

confidence: 99%

Admission Levels of C-Reactive Protein and Plasminogen Activator Inhibitor-1 in Patients With Acute Myocardial Infarction With and Without Cardiogenic Shock or Heart Failure on Admission

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Many studies now show the importance of CRP levels as a predictive factor in cardiac disease both for the occurrence of a coronary event (35,36) and postmyocardial infarct survival (37,38). CRP has been shown to colocalize with complement in acute myocardial infarction (39) and together they have been demonstrated to be important mediators of the resulting tissue damage (2,36). Inhibition of the early phase of complement activation has been demonstrated in an animal model to have cardioprotective effects following ischemia/reperfusion injury (40), and using complement inhibition as a therapy is the subject of many studies (reviewed in Refs.…”

Section: Discussionmentioning

confidence: 99%

Evidence That Complement Protein C1q Interacts with C-Reactive Protein through Its Globular Head Region

McGrath

Brouwer

Arlaud

et al. 2006

The Journal of Immunology

118

101

View full text Add to dashboard Cite

C1q acts as the recognition unit of the first complement component, C1, and binds to immunoglobulins IgG and IgM, as well as to non-Ig ligands, such as C-reactive protein (CRP). IgG and IgM are recognized via the globular head regions of C1q (C1qGR), whereas CRP has been postulated to interact with the collagen-like region (C1qCLR). In the present study, we used a series of nine mAbs to C1q, five directed against C1qGR and four against C1qCLR, to inhibit the interaction of C1q with CRP. The F(ab′)2 of each of the five mAbs directed against C1qGR inhibited binding of C1q to polymerized IgG. These five mAbs also successfully inhibited the interaction of C1q with CRP. Moreover, these five mAbs inhibited C1 activation by CRP as well as by polymerized IgG in vitro. In contrast, none of the four mAbs against C1qCLR inhibited C1q interaction with CRP or IgG, or could reduce activation of complement by CRP or polymerized IgG. These results provide the first evidence that the interaction of C1q with CRP or IgG involves sites located in the C1qGR, whereas sites in the CLR do not seem to be involved in the physiological interaction of C1q with CRP.

show abstract

“…The complement cascade is activated through three distinct mechanisms designated the classical, alternative and lectin pathways [24], [25]. Numerous studies have indicated that ischemic myocardial injury activates the complement cascade [26].…”

Section: The Complement Cascadementioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

572

499

View full text Add to dashboard Cite

Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll Like Receptor-mediated pathways, the complement cascade and reactive oxygen generation induce Nuclear Factor (NF)-κB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming Growth Factor (TGF)-β plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding the role of the immune system in cardiac repair is necessary in order to design optimal strategies for cardiac regeneration.

show abstract

CRP, a major culprit in complement-mediated tissue damage in acute myocardial infarction?

Cited by 42 publications

References 85 publications

Admission Levels of C-Reactive Protein and Plasminogen Activator Inhibitor-1 in Patients With Acute Myocardial Infarction With and Without Cardiogenic Shock or Heart Failure on Admission

Admission Levels of C-Reactive Protein and Plasminogen Activator Inhibitor-1 in Patients With Acute Myocardial Infarction With and Without Cardiogenic Shock or Heart Failure on Admission

Evidence That Complement Protein C1q Interacts with C-Reactive Protein through Its Globular Head Region

The immune system and cardiac repair

Contact Info

Product

Resources

About