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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2(2),76-86;2009
Original Article
Substance P is required for the pathogenesis of EMCV infection in mice
Prema Robinson, Armandina Garza, Jeffrey Moore, T. Kris Eckols, Skakun Parti, Vishwanathan Balaji, Jesus Vallejo, David J. Tweardy
Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA;
CHRISTUS St John Hospital, 18300 St John Drive, Nassau Bay, TX 77058, USA; Department of Pediatrics, Section of Infectious
Diseases, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas 77030, USA.
Received February 24, 2009; accepted March 26, 2009; available online March 31, 2009
Abstract: Myocarditis is an important cause of heart failure in adolescents and young adults and is caused, most commonly, by viral
infections. Viral myocarditis is characterized by cardiac inflammation and cardiomyocyte necrosis. The molecular pathogenesis of viral
myocarditis is incomplete and specific therapies are not available. Proinflammatory cytokines such as IL-1β, TNF-α and IL-6 have been
implicated in the pathogenesis of myocarditis caused by encephalomyocarditis virus (EMCV) infection, a model of viral myocarditis in
mice. Substance P (SP), a neuropeptide and pain transmitter, stimulates the production of proinflammatory cytokines and has been
demonstrated by us and others to contribute to the pathogenesis of several viral, protozoan and helminth infections in mouse and man.
Receptors for SP are expressed on the surface of cardiomyocytes, neurons, endothelial cells and immunocytes, including lymphocytes
and macrophages. The current studies were performed to evaluate the role of SP in the pathogenesis of EMCV-induce myocarditis. SP
levels were increased 61 fold in EMCV infected wild-type mice. EMCV infection resulted in 51% mortality at 14 days and a 1.56 fold
increase in heart-to-body weight ratio that was accompanied by cardiac inflammation and necrosis and along with cardiomyocyte
apoptosis and hypertrophy of surviving cells. In contrast, SP precursor knockout mice were completely protected from EMCV-mortality,
cardiomegaly, cardiac inflammation and necrosis as well as cardiomyocyte apoptosis and hypertrophy. These results indicate that SP
is essential for the pathogenesis of EMCV myocarditis and suggest that targeting this signaling pathway may be beneficial in viral
myocarditis in humans. (IJCEM902005).
Key Words: Substance-P, myocarditis, pathogenesis, encephalomyocarditis-virus
Full Text PDF
Address all correspondence to:
Prema Robinson, PhD
Section of Infectious Diseases, Department of Medicine
Baylor College of Medicine
One Baylor Plaza, Room 535EB
Houston, Texas 77030
Tel: 713-798-6848, Fax: 713-790-0681
E-mail: premar@bcm.tmc.edu
Original Article
Substance P is required for the pathogenesis of EMCV infection in mice
Prema Robinson, Armandina Garza, Jeffrey Moore, T. Kris Eckols, Skakun Parti, Vishwanathan Balaji, Jesus Vallejo, David J. Tweardy
Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA;
CHRISTUS St John Hospital, 18300 St John Drive, Nassau Bay, TX 77058, USA; Department of Pediatrics, Section of Infectious
Diseases, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas 77030, USA.
Received February 24, 2009; accepted March 26, 2009; available online March 31, 2009
Abstract: Myocarditis is an important cause of heart failure in adolescents and young adults and is caused, most commonly, by viral
infections. Viral myocarditis is characterized by cardiac inflammation and cardiomyocyte necrosis. The molecular pathogenesis of viral
myocarditis is incomplete and specific therapies are not available. Proinflammatory cytokines such as IL-1β, TNF-α and IL-6 have been
implicated in the pathogenesis of myocarditis caused by encephalomyocarditis virus (EMCV) infection, a model of viral myocarditis in
mice. Substance P (SP), a neuropeptide and pain transmitter, stimulates the production of proinflammatory cytokines and has been
demonstrated by us and others to contribute to the pathogenesis of several viral, protozoan and helminth infections in mouse and man.
Receptors for SP are expressed on the surface of cardiomyocytes, neurons, endothelial cells and immunocytes, including lymphocytes
and macrophages. The current studies were performed to evaluate the role of SP in the pathogenesis of EMCV-induce myocarditis. SP
levels were increased 61 fold in EMCV infected wild-type mice. EMCV infection resulted in 51% mortality at 14 days and a 1.56 fold
increase in heart-to-body weight ratio that was accompanied by cardiac inflammation and necrosis and along with cardiomyocyte
apoptosis and hypertrophy of surviving cells. In contrast, SP precursor knockout mice were completely protected from EMCV-mortality,
cardiomegaly, cardiac inflammation and necrosis as well as cardiomyocyte apoptosis and hypertrophy. These results indicate that SP
is essential for the pathogenesis of EMCV myocarditis and suggest that targeting this signaling pathway may be beneficial in viral
myocarditis in humans. (IJCEM902005).
Key Words: Substance-P, myocarditis, pathogenesis, encephalomyocarditis-virus
Full Text PDF
Address all correspondence to:
Prema Robinson, PhD
Section of Infectious Diseases, Department of Medicine
Baylor College of Medicine
One Baylor Plaza, Room 535EB
Houston, Texas 77030
Tel: 713-798-6848, Fax: 713-790-0681
E-mail: premar@bcm.tmc.edu
