Intercellular adhesion molecule 1 (ICAM-1) - A new substrate for the development of ventricular fibrillation?

Abstract

Screening patients of an increased risk to develop ventricular fibrillation (VF) is of utmost medical interest [1], because VF might cause sudden cardiac death accounting for almost half of all cardiovascular deaths [2]. Primary VF most commonly occurs under circumstances of acute myocardial infarction (AMI) [3]. Clinical risk factors for the development of VF have been identified [4]. Contributing factors to VF such as genetic polymorphisms [5], inflammatory and coagulatory markers are increasingly focused [6–11]. The intercellular adhesion molecule 1 (ICAM-1) is located on the surface of white blood cells, macrophages, lymphocytes and endothelial cells and plays an important rolewithin inflammatory processes such as atherosclerosis [12,13]. Atherosclerosis develops as part of an inflammatory response either to endothelial cell injury or to the retention of subendothelial cholesterol-rich, atherogenic lipoproteins [14]. Specifically, interactions between neutrophils and the endothelium arise consisting in the rolling along the post-capillary venules and extravasation of leukocytes, which is stepwise mediated through selectins, integrins and ICAM molecules [15,16]. Soluble ICAM-1 (sICAM-1) in serum was shown to be up-regulated during AMI [17] and during ventricular reperfusion arrhythmias after coronary angioplasty [18]. For the present study, a possible subclinical inflammatory state, represented by the expression of ICAM-1mRNA of human blood cells or sICAM-1 in serum during follow-up after VF, was hypothesized in patients suffering from ischemia-related VF [11]. Within a retrospective observational study 90patientswithfirst AMI were included. 43 patients had VF (VF+) in the initial phase of AMI not related to coronary reperfusion. 47 patients presentedwithAMIwithout VF (VF−). Diagnosis of AMI was based on typical symptoms and signs according to ESC guidelines [19,20]. Coronary angiography was performed within 24 h after onset of symptoms. VF was either documented outside the hospital by paramedics or in the intensive care unit prior to percutaneous coronary intervention. Most of the patients with VF during AMI were resuscitated outside the hospital. Blood samples were taken remote from AMI with a median of 634 days. All patients were clinically asymptomatic at the time of blood sampling. Written informed consent was obtained from all patients. The study protocol was approved by the medical ethics commission II of theMedical FacultyMannheim, University of Heidelberg, Germany. RNA was prepared from whole blood containing all types of human blood cells (PAXgeneTM Blood tubes, PreAnalytiX, Germany). Quantification of ICAM-1 mRNA expression was done by real-time RT-PCR (RTqPCR) using the ΔΔCT method with GAPDH as housekeeping gene for normalization. Serum levels of sICAM-1 were measured by a commercially available enzyme-linked immunosorbent assay (Quantikine® Human sICAM-1/CD54 Immunoassay, R&D Systems). The calculations were performed with InStat (GraphPad, USA) and IBM SPSS (IBM SPSS, Germany). Patients' characteristics are summarized in Table 1. (VF+) patients revealed 48% lower ICAM-1 mRNA expression in human blood cells