Increase Of Mobilization Of Bone Marrow-Derived Cells In Acute Viral Myocarditis Induced By Coxsackie Virus B3

Objectives: Bone marrow-derived cells(BMC)were recently identified to play a vital role in repairing damaged myocardium.However,it is yet unknown whether the mobilization of BMCs is involved in the pathogenesis of virus-induced acute myocarditis(VMC).Thus,we aimed to analyze the expression of CD45~+CD34~+VLA-4~+cells,and vascular cell adhesion protein-1(VCAM-1)in a murine model of acute VMC.Methods: Male BALB/c mice were intraperitoneally infected coxsackievirus B3(CVB3)to establish acute VMC.Frequency ofCD45~+CD34~+VLA-4~+cells in the heart,peripheral blood and bone marrow were examined by flow cytometry on day3,day7,day14 and day28 post injections.Cardiac VCAM-1 and pathology scores were determined by immunohistochemistry and myocardial VCAM-1,IL-1? and TNF-? were analyzed by RT-PCR and Western-blotting.Results: CD45~+CD34~+VLA-4~+cells populations were significantlyincreased in CVB3-infected acute VMC mice heart compared to healthy controls from 7 day,then decreased at 2week and 4week(P<0.05).In extracted bone marrow and peripheral blood the percentage of CD34~+VLA-4~+ cells was decreased in acute VCM mice in comparison to controls at 3 day(P?0.05),then gradually increased and reached a maximum at 7day,then decreased at 2week and 4week(P<0.05).We found an enhanced migration of CD45~+CD34~+VLA-4~+cells to the diseased heart over-expressing VCAM-1.Immunohistochemical showing a higher expression of VCAM-1 in acute VCM hearts than healthy control mice,even more neovascularization of inflammatory cells around.The expression of IL-1? and TNF-? inflammatory factor and VCAM-1 homing factor mRNA and protein significantly increased in infected mice than healthy control mice at each time point(P<0.05).VCAM-1 homing factor were paralleling mobilized CD45~+CD34~+VLA-4~+cells in the heart.It showed that VCAM-1 was highly promoting CD45~+CD34~+VLA-4~+cells mobilization into the damage heart.Cardiac inflammatory factor and pathology scores were not paralleling mobilized CD45~+CD34~+VLA-4~+cells in the heart.Conclusions: In acute VMC mice,VCAM-1 might promote CD45~+CD34~+VLA-4~+cells mobilization into the damaged heart,which was involved in the repair of injured myocardial pathogenesis.