TY - JOUR
T1 - Myocarditis induced by targeted expression of the MCP-1 gene in murine cardiac muscle
AU - Kolattukudy, Pappachan E.
AU - Quach, Tam
AU - Bergese, Sergio
AU - Breckenridge, Suzanne
AU - Hensley, James
AU - Altschuld, Ruth
AU - Gordillo, Gayle
AU - Klenotic, Shelley
AU - Orosz, Charles
AU - Parker-Thornburg, Jan
PY - 1998/1
Y1 - 1998/1
N2 - To explore the possible role of monocyte chemotactic protein (MCP-1) in inflammatory diseases of the heart, we expressed the murine MCP-1(JE) gene under the control of the α-cardiac myosin heavy chain promoter to attempt to target MCP-1 expression to the adult heart muscle. The five lines of transgenic mice thus produced showed targeted expression of MCP-1 transcripts and protein in the adult heart muscle and pulmonary vein but not in skeletal muscle. MCP-1 level in the transgenic hearts increased up to 30 to 45 days of age, and leukocyte infiltration into interstitium between cardiomyocytes increased up to 60 to 75 days. The infiltrate was mainly macrophages but not T cells. The presence of MCP-1 in the transgenic hearts did not induce cytokine production indicative of leukocyte activation. Echocardiographic analysis of 1-year-old mice that express MCP-1 in the myocardium and of age- matched controls revealed cardiac hypertrophy and dilation, increases in left ventricular (LV) mass, and systolic and diastolic left ventricular internal diameters. A significant decline in M-mode shortening fraction showed depressed contractile function. Transgenic hearts were 65% heavier, and histological analysis showed moderate myocarditis, edema, and some fibrosis. Thus, MCP-1 expression in the heart muscle may provide a model to investigate myocarditis and cardiomyopathy.
AB - To explore the possible role of monocyte chemotactic protein (MCP-1) in inflammatory diseases of the heart, we expressed the murine MCP-1(JE) gene under the control of the α-cardiac myosin heavy chain promoter to attempt to target MCP-1 expression to the adult heart muscle. The five lines of transgenic mice thus produced showed targeted expression of MCP-1 transcripts and protein in the adult heart muscle and pulmonary vein but not in skeletal muscle. MCP-1 level in the transgenic hearts increased up to 30 to 45 days of age, and leukocyte infiltration into interstitium between cardiomyocytes increased up to 60 to 75 days. The infiltrate was mainly macrophages but not T cells. The presence of MCP-1 in the transgenic hearts did not induce cytokine production indicative of leukocyte activation. Echocardiographic analysis of 1-year-old mice that express MCP-1 in the myocardium and of age- matched controls revealed cardiac hypertrophy and dilation, increases in left ventricular (LV) mass, and systolic and diastolic left ventricular internal diameters. A significant decline in M-mode shortening fraction showed depressed contractile function. Transgenic hearts were 65% heavier, and histological analysis showed moderate myocarditis, edema, and some fibrosis. Thus, MCP-1 expression in the heart muscle may provide a model to investigate myocarditis and cardiomyopathy.
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M3 - Article
C2 - 9422528
AN - SCOPUS:0031963714
SN - 0002-9440
VL - 152
SP - 101
EP - 111
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -