Biomedical subjects

Remco Nijmeijer

Publications and source records attributed to Remco Nijmeijer.

3 recordsLinked to original sources

PubMed2006

Inhibition of sPLA2-IIA, C-reactive protein or complement: new therapy for patients with acute myocardial infarction?

Reperfusion of ischemic myocardium after acute myocardial infarction (AMI) induces a local activation of inflammatory reactions that results in ischemia/reperfusion (I/R)-injury. I/R-injury contributes considerably to the total cell damage in the heart after AMI. Secretory phospolipase A2-IIA (sPLA2-IIA), C-reactive protein (CRP) and complement are inflammatory mediators that have been demonstrated to play key roles in I/R injury. From studies by us and others a mechanism emerged in which sPLA2-IIA binds to reversibly damaged cardiomyocytes and subsequently induces cell death, partly by potentiating binding of CRP and subsequent complement activation. Next to this, sPLA2-IIA also has a direct toxic effect, independent of CRP or complement. Therefore, these studies indicate a crucial role of inflammatory mediators in ischemia/reperfusion injury. This review will focus on the pathogenic effects of sPLA2-IIA, CRP and complement and on the putative therapeutic effects of inhibitors of these inflammatory mediators in acute myocardial infarction.

Animals↗

PubMed2003

C-reactive protein activates complement in infarcted human myocardium.

Circulating levels of C-reactive protein (CRP) constitute a cardiovascular risk marker. Immunohistochemical studies have revealed co-localization of CRP and activated complement in human infarcted myocardium suggesting CRP to enhance inflammation in ischemic myocardium by inducing local complement activation. The aim was to establish whether CRP activates complement in infarcted human myocardium and to assess the relationship between this activation and the duration of infarction. Myocardial tissue samples from 56 patients that had died from acute myocardial infarction were evaluated. Specimens were taken from infarcted as well as noninfarcted sites of the heart. CRP-mediated complement activation was assessed by immunohistochemistry and by measuring levels of complement, CRP, and CRP-complement complexes, specific markers for CRP-mediated activation, in homogenates of the heart. Infarctions of 12 hours to 5 days had significantly more extensive depositions of complement and CRP and contained significantly more CRP, activated complement, and CRP-complement complexes than infarctions that were less than 12 hours old. Levels of CRP complexes correlated significantly with CRP and complement concentrations in the infarctions, as well as with the extent of complement and CRP depositions as measured via immunohistochemistry. Specific activation products of CRP-mediated activation of complement are increased in infarcts of more than 12 hours in duration and correlate with the extent of complement depositions. Hence, CRP seems to enhance local inflammatory reactions ensuing in human myocardial infarcts of more than 12 hours duration.

C-Reactive Protein↗

PubMed2002

Secretory type II phospholipase A(2) binds to ischemic myocardium during myocardial infarction in humans.

OBJECTIVE: An increase of circulating secretory Phospholipase A(2) (sPLA(2)) is a risk factor for coronary artery disease. We hypothesized that this reflects participation of sPLA(2) in local inflammatory reactions ensuing in ischemic myocardium. Therefore, we studied the course of circulating sPLA(2), in patients with acute myocardial infarction (AMI) or unstable angina pectoris (UAP), and investigated the presence of sPLA(2) in infarcted myocardial tissue. METHODS: Plasma samples of 107 patients with AMI or UAP, collected on admission and at varying intervals thereafter, were tested for the presence of sPLA(2) and C-reactive protein (CRP). Cumulative release values of these parameters were calculated, which allowed for comparison of the results rearranged in time according to the onset of symptoms. By immunohistochemistry we studied the presence of sPLA(2) and CRP in myocardial tissue of 30 patients who died subsequent to AMI. RESULTS: Levels of sPLA(2) became elevated during the disease course in 66 of the 87 patients with AMI, and were higher than those of the patients with UAP of whom 8 of the 20 had elevated levels. By immunohistochemistry sPLA(2) was found to be localized in the infarcted myocardium, particularly in its borderzone, from 12 h after the onset of AMI. Positive staining for sPLA(2) was more extensive than that for CRP. CONCLUSIONS: The localization pattern of sPLA(2) in infarcted myocardium as well as its plasma course, in relation to those of CRP, are in line with a supposed pro-inflammatory role during AMI for sPLA(2) as a generator of lysophospholipids serving as ligands for CRP.

Angina, Unstable↗