TY - JOUR
T1 - Quantitative Analysis of Myocardial Inflammation by Flow Cytometry in Murine Autoimmune Myocarditis
T2 - Correlation with Cardiac Function
AU - Afanasyeva, Marina
AU - Georgakopoulos, Dimitrios
AU - Belardi, Diego F.
AU - Ramsundar, Amrish C.
AU - Barin, Jobert G.
AU - Kass, David A.
AU - Rose, Noel R.
PY - 2004/3
Y1 - 2004/3
N2 - Inflammation has been increasingly recognized as an important pathological component of heart failure. Existing methods of assessing myocardial infiltrate are labor-intensive and provide data that are difficult to quantify and not representative of the whole heart. As a result, little effort has been made to systematically assess the components of myocardial inflammation. We established an alternative method of quantitative assessment of myocardial inflammation by flow cytometry after enzymatic digestion of hearts to characterize the infiltrate and study the association between inflammation and cardiac function in murine experimental autoimmune myocarditis. The severity of acute myocarditis uniquely correlated with the proportion of neutrophils, but not T cells, B cells, or macrophages. Both acute and chronic phases were characterized by the presence of CD44high (activated) T cells in the heart, whereas T cells trafficking through normal hearts exhibited CD44 low phenotype. During the chronic phase, the proportion of CD4 + T cells was associated with increased left-ventricular volumes and deterioration of systolic function, the hallmarks of dilated cardiomyopathy. We conclude that flow cytometry on uniformly digested mouse hearts provides sensitive and reproducible assessment of myocardial infiltrate and can be used to dissect out the specific role of individual immune components from the overall inflammatory response in the heart.
AB - Inflammation has been increasingly recognized as an important pathological component of heart failure. Existing methods of assessing myocardial infiltrate are labor-intensive and provide data that are difficult to quantify and not representative of the whole heart. As a result, little effort has been made to systematically assess the components of myocardial inflammation. We established an alternative method of quantitative assessment of myocardial inflammation by flow cytometry after enzymatic digestion of hearts to characterize the infiltrate and study the association between inflammation and cardiac function in murine experimental autoimmune myocarditis. The severity of acute myocarditis uniquely correlated with the proportion of neutrophils, but not T cells, B cells, or macrophages. Both acute and chronic phases were characterized by the presence of CD44high (activated) T cells in the heart, whereas T cells trafficking through normal hearts exhibited CD44 low phenotype. During the chronic phase, the proportion of CD4 + T cells was associated with increased left-ventricular volumes and deterioration of systolic function, the hallmarks of dilated cardiomyopathy. We conclude that flow cytometry on uniformly digested mouse hearts provides sensitive and reproducible assessment of myocardial infiltrate and can be used to dissect out the specific role of individual immune components from the overall inflammatory response in the heart.
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U2 - 10.1016/S0002-9440(10)63169-0
DO - 10.1016/S0002-9440(10)63169-0
M3 - Article
C2 - 14982835
AN - SCOPUS:1242316277
SN - 0002-9440
VL - 164
SP - 807
EP - 815
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -