BACKGROUND: Matrix metalloproteinase (MMP) activity is upregulated in the hearts with myocarditis, and its activation contributes to the changes in left ventricular function. A major macrolide antibiotic, clarithromycin (CAM), has many biological functions including MMP regulation. However, little is known about the effect of CAM in myocarditis via MMPs. OBJECTIVE: To clarify the role of MMPs regulated by CAM in the progression of myocarditis. Design CAM was given to experimental rats with autoimmune myocarditis (EAM) from day -7 to day 21 (early treated group, n=6) or from day 1 to day 21 (late treated group, n=6) twice a day. RESULTS: Although the non-treated rats showed blood pressure decline and impaired cardiac function, early CAM treatment prevented this progression. Pathologically, severe myocardial cell infiltration (30.5+/-4.2%) and fibrosis (32.2+/-1.1%) were detected in the non-treated group, while early CAM treatment significantly suppressed these changes (infiltration 6.5+/-0.2%, fibrosis 5.9+/-3.9%). Zymography showed that non-treated EAM resulted in enhanced ventricular activities of MMP-9, while early CAM treatment reduced the alteration. However, late CAM treatment was less effective than the early treatment. CONCLUSIONS: Early CAM treatment is effective to attenuate myocarditis by suppressing MMP-9.
BACKGROUND: Matrix metalloproteinase (MMP) activity is upregulated in the hearts with myocarditis, and its activation contributes to the changes in left ventricular function. A major macrolide antibiotic, clarithromycin (CAM), has many biological functions including MMP regulation. However, little is known about the effect of CAM in myocarditis via MMPs. OBJECTIVE: To clarify the role of MMPs regulated by CAM in the progression of myocarditis. Design CAM was given to experimental rats with autoimmune myocarditis (EAM) from day -7 to day 21 (early treated group, n=6) or from day 1 to day 21 (late treated group, n=6) twice a day. RESULTS: Although the non-treated rats showed blood pressure decline and impaired cardiac function, early CAM treatment prevented this progression. Pathologically, severe myocardial cell infiltration (30.5+/-4.2%) and fibrosis (32.2+/-1.1%) were detected in the non-treated group, while early CAM treatment significantly suppressed these changes (infiltration 6.5+/-0.2%, fibrosis 5.9+/-3.9%). Zymography showed that non-treated EAM resulted in enhanced ventricular activities of MMP-9, while early CAM treatment reduced the alteration. However, late CAM treatment was less effective than the early treatment. CONCLUSIONS: Early CAM treatment is effective to attenuate myocarditis by suppressing MMP-9.
Authors: Pablo Nakagawa; Yunhe Liu; Tang-Dong Liao; Xiaojuan Chen; Germán E González; Kevin R Bobbitt; Derek Smolarek; Ed L Peterson; Ross Kedl; Xiao-Ping Yang; Nour-Eddine Rhaleb; Oscar A Carretero Journal: Am J Physiol Heart Circ Physiol Date: 2012-08-24 Impact factor: 4.733
Authors: Marian Kacerovsky; Roberto Romero; Martin Stepan; Jaroslav Stranik; Jan Maly; Lenka Pliskova; Radka Bolehovska; Vladimir Palicka; Helena Zemlickova; Helena Hornychova; Jiri Spacek; Bo Jacobsson; Percy Pacora; Ivana Musilova Journal: Am J Obstet Gynecol Date: 2020-07 Impact factor: 10.693