tetano
Editor, Senior Moderator
Am J Physiol Heart Circ Physiol. 2014 Jul 18. pii: ajpheart.00076.2014. [Epub ahead of print]
Ectopic trypsin in the myocardium promotes dilated cardiomyopathy after influenza A virus infection.
Pan HY1, Sun HM1, Xue LJ1, Pan M1, Wang YP1, Kido H2, Zhu JH3.
Author information
Abstract
We previously reported ectopic trypsin in the myocardium triggers acute myocarditis after influenza A virus (IAV) infection. As myocarditis is a common precursor to dilated cardiomyopathy (DCM), the aim of this study was to investigate the influence of trypsin on progression of DCM after IAV infection. IAV-infected mice treated with saline or trypsin inhibitor were euthanized at day 0, 9, 20, 40 and 60 post infection. Trypsin expression colocalized with myocardial inflammatory loci and IAV-induced myocarditis peaked at day 9 post infection and alleviated by day 20, but persisted until day 60 post infection, even though replication of IAV was not detected from day 20 post infection. Similar time courses were observed for activation of promatrix metalloproteinase (proMMP)-9 and expression of proinflammatory cytokines interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α. Degradation of collagen I (Col I), proliferation of ventricular interstitial collagen and expression of Col I and Col III mRNA increased significantly during acute and chronic phases; Col III mRNA increased more significantly than Col I mRNA. Cardiac function progressively deteriorated with progressive left ventricular dilation. The trypsin inhibitor aprotinin suppressed proMMP-9 activation and cytokine release, alleviated myocardial inflammation and restored collagen metabolism during acute and chronic phases of myocarditis. This effectively prevented ventricular dilation and improved cardiac function. These results suggested ectopic trypsin in the myocardium promoted DCM through chronic activation of proMMP-9, persistent induction of cytokines and mediation of collagen remodeling. Pharmacologic inhibition of trypsin activity might be a promising approach for prevention of viral cardiomyopathy.
Copyright ? 2014, American Journal of Physiology - Heart and Circulatory Physiology.
KEYWORDS:
dilated cardiomyopathy; extracellular matrix remodeling; influenza virus; myocarditis; trypsin
PMID:
25038143
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25038143
Ectopic trypsin in the myocardium promotes dilated cardiomyopathy after influenza A virus infection.
Pan HY1, Sun HM1, Xue LJ1, Pan M1, Wang YP1, Kido H2, Zhu JH3.
Author information
Abstract
We previously reported ectopic trypsin in the myocardium triggers acute myocarditis after influenza A virus (IAV) infection. As myocarditis is a common precursor to dilated cardiomyopathy (DCM), the aim of this study was to investigate the influence of trypsin on progression of DCM after IAV infection. IAV-infected mice treated with saline or trypsin inhibitor were euthanized at day 0, 9, 20, 40 and 60 post infection. Trypsin expression colocalized with myocardial inflammatory loci and IAV-induced myocarditis peaked at day 9 post infection and alleviated by day 20, but persisted until day 60 post infection, even though replication of IAV was not detected from day 20 post infection. Similar time courses were observed for activation of promatrix metalloproteinase (proMMP)-9 and expression of proinflammatory cytokines interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α. Degradation of collagen I (Col I), proliferation of ventricular interstitial collagen and expression of Col I and Col III mRNA increased significantly during acute and chronic phases; Col III mRNA increased more significantly than Col I mRNA. Cardiac function progressively deteriorated with progressive left ventricular dilation. The trypsin inhibitor aprotinin suppressed proMMP-9 activation and cytokine release, alleviated myocardial inflammation and restored collagen metabolism during acute and chronic phases of myocarditis. This effectively prevented ventricular dilation and improved cardiac function. These results suggested ectopic trypsin in the myocardium promoted DCM through chronic activation of proMMP-9, persistent induction of cytokines and mediation of collagen remodeling. Pharmacologic inhibition of trypsin activity might be a promising approach for prevention of viral cardiomyopathy.
Copyright ? 2014, American Journal of Physiology - Heart and Circulatory Physiology.
KEYWORDS:
dilated cardiomyopathy; extracellular matrix remodeling; influenza virus; myocarditis; trypsin
PMID:
25038143
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25038143