Peter Alter1, Heinz Rupp, Bernhard Maisch. 1. Philipps University of Marburg, Department of Internal Medicine-Cardiology, Germany. palter@med.uni-marburg.de
Abstract
OBJECTIVES AND BACKGROUND: Myocarditis is caused by various agents and autoimmune processes. It is unknown whether viral genome persistence represents inactive remnants of previous infections or whether it is attributed to ongoing adverse processes. The latter also applies to the course of autoimmune myocarditis. One principal candidate for an adverse remodeling is nuclear factor-kappaB (NFkappaB). METHODS: A total of 93 patients with suspected myocarditis/cardiomyopathy was examined. Hemodynamics were assessed by echocardiography as well as right and left heart catheterization. Endomyocardial biopsies were taken from the left ventricle. Biopsies were examined by immunohistochemistry and PCR for viral genomes. Selective immunostaining of activated NFkappaB was performed. RESULTS: NFkappaB was increased in patients with myocarditis when compared with controls (11.1+/-7.1% vs. 5.0+/-5.3%, P<0.005) whereas dilated cardiomyopathy showed no significant increase. Patients with myocarditis and preserved left ventricular function exhibited increased activated NFkappaB when compared with reduced function (r2=0.72, P<0.001). In parallel, inverse correlation of NFkappaB and left ventricular enddiasstolic volume was found (r2=0.43, P<0.02). Increased activated NFkappaB was found in adenovirus persistence when compared with controls (P=0.001). Only a trend of increased NFkappaB activation was seen in cytomegalovirus persistence. Parvovirus B19 persistence did not affect NFkappaB activation. CONCLUSIONS: Increased activation of NFkappaB is related to inflammatory processes in myocarditis. Since activated NFkappaB correlates with left ventricular function, it could be assumed that NFkappaB activation occurs at early stages of inflammation. Potentially, NFkappaB could inhibit loss of cardiomyocytes by apoptosis and protect from cardiac dilation. Since NFkappaB is a crucial key transcription factor of inflammation, its prognostic and future therapeutic relevance should be addressed.
OBJECTIVES AND BACKGROUND:Myocarditis is caused by various agents and autoimmune processes. It is unknown whether viral genome persistence represents inactive remnants of previous infections or whether it is attributed to ongoing adverse processes. The latter also applies to the course of autoimmune myocarditis. One principal candidate for an adverse remodeling is nuclear factor-kappaB (NFkappaB). METHODS: A total of 93 patients with suspected myocarditis/cardiomyopathy was examined. Hemodynamics were assessed by echocardiography as well as right and left heart catheterization. Endomyocardial biopsies were taken from the left ventricle. Biopsies were examined by immunohistochemistry and PCR for viral genomes. Selective immunostaining of activated NFkappaB was performed. RESULTS:NFkappaB was increased in patients with myocarditis when compared with controls (11.1+/-7.1% vs. 5.0+/-5.3%, P<0.005) whereas dilated cardiomyopathy showed no significant increase. Patients with myocarditis and preserved left ventricular function exhibited increased activated NFkappaB when compared with reduced function (r2=0.72, P<0.001). In parallel, inverse correlation of NFkappaB and left ventricular enddiasstolic volume was found (r2=0.43, P<0.02). Increased activated NFkappaB was found in adenovirus persistence when compared with controls (P=0.001). Only a trend of increased NFkappaB activation was seen in cytomegalovirus persistence. Parvovirus B19 persistence did not affect NFkappaB activation. CONCLUSIONS: Increased activation of NFkappaB is related to inflammatory processes in myocarditis. Since activated NFkappaB correlates with left ventricular function, it could be assumed that NFkappaB activation occurs at early stages of inflammation. Potentially, NFkappaB could inhibit loss of cardiomyocytes by apoptosis and protect from cardiac dilation. Since NFkappaB is a crucial key transcription factor of inflammation, its prognostic and future therapeutic relevance should be addressed.
Authors: Harald J Maier; Tobias G Schips; Astrid Wietelmann; Marcus Krüger; Cornelia Brunner; Martina Sauter; Karin Klingel; Thomas Böttger; Thomas Braun; Thomas Wirth Journal: Proc Natl Acad Sci U S A Date: 2012-07-02 Impact factor: 11.205
Authors: P Alter; H Rupp; M B Rominger; A Vollrath; F Czerny; J H Figiel; P Adams; F Stoll; K J Klose; B Maisch Journal: Mol Cell Biochem Date: 2008-05-07 Impact factor: 3.396