TY - JOUR
T1 - CNP infusion attenuates cardiac dysfunction and inflammation in myocarditis
AU - Obata, Hiroaki
AU - Yanagawa, Bobby
AU - Tanaka, Koichi
AU - Ohnishi, Shunsuke
AU - Kataoka, Masaharu
AU - Miyahara, Yoshinori
AU - Ishibashi-Ueda, Hatsue
AU - Kodama, Makoto
AU - Aizawa, Yoshifusa
AU - Kangawa, Kenji
AU - Nagaya, Noritoshi
PY - 2007/4/27
Y1 - 2007/4/27
N2 - Myocarditis is an acute inflammatory disease of the myocardium for which there is currently no specific therapy. We investigated the therapeutic potential of C-type natriuretic peptide (CNP) in acute experimental autoimmune myocarditis. One week after injection of porcine myosin into male Lewis rats, CNP (0.05 μg/kg/min) was continuously administered for 2 weeks. CNP infusion significantly increased maximum dP/dt, decreased left ventricular end-diastolic pressure, and improved fractional shortening compared with vehicle administration. In vehicle-treated hearts, severe necrosis and marked infiltration of CD68-positive inflammatory cells were observed. Myocardial and serum levels of monocyte chemoattractant protein-1 were elevated in myocarditis. However, these changes were attenuated by CNP infusion. In addition, treatment with CNP significantly increased myocardial capillary density. Guanylyl cyclase-B, a receptor for CNP, was expressed in myocarditic heart, and cyclic guanosine monophosphate was elevated by CNP infusion. In conclusion, CNP infusion attenuated cardiac function in acute myocarditis through anti-inflammatory and angiogenic effects.
AB - Myocarditis is an acute inflammatory disease of the myocardium for which there is currently no specific therapy. We investigated the therapeutic potential of C-type natriuretic peptide (CNP) in acute experimental autoimmune myocarditis. One week after injection of porcine myosin into male Lewis rats, CNP (0.05 μg/kg/min) was continuously administered for 2 weeks. CNP infusion significantly increased maximum dP/dt, decreased left ventricular end-diastolic pressure, and improved fractional shortening compared with vehicle administration. In vehicle-treated hearts, severe necrosis and marked infiltration of CD68-positive inflammatory cells were observed. Myocardial and serum levels of monocyte chemoattractant protein-1 were elevated in myocarditis. However, these changes were attenuated by CNP infusion. In addition, treatment with CNP significantly increased myocardial capillary density. Guanylyl cyclase-B, a receptor for CNP, was expressed in myocarditic heart, and cyclic guanosine monophosphate was elevated by CNP infusion. In conclusion, CNP infusion attenuated cardiac function in acute myocarditis through anti-inflammatory and angiogenic effects.
KW - Angiogenesis
KW - Inflammation
KW - MCP-1
KW - Myocarditis
KW - Natriuretic peptides
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U2 - 10.1016/j.bbrc.2007.02.085
DO - 10.1016/j.bbrc.2007.02.085
M3 - Article
C2 - 17336931
AN - SCOPUS:33947103522
SN - 0006-291X
VL - 356
SP - 60
EP - 66
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -