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(Circulation. 2001;104:275.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Human Coxsackie-Adenovirus Receptor Is Colocalized With Integrins 
vß3 and vß5 on the Cardiomyocyte Sarcolemma and Upregulated in Dilated Cardiomyopathy
Implications for Cardiotropic Viral Infections
From the Department of Cardiology and Pneumology, University Hospital Benjamin Franklin, Freie Universität, Berlin, Germany (M.N., H.F., X.W., M.P., H.-P.S., W.P.); the Departments of Biochemistry (H.d.J., D.D., J.L.) and Pathology (A.B.H.), Cardiovasculair Onderzoeksinstituut Erasmus Universiteit Rotterdam, Faculty of Medicine and Health Sciences, Erasmus Universiteit, Rotterdam, the Netherlands; Children’s Hospital of Philadelphia, Philadelphia, Pa (J.B.); the National Heart and Lung Institute of Imperial College, Middlesex, UK (R.W., M.Y.); and the Deutsches Herzzentrum, Berlin, Germany (R.H.).
Correspondence to Prof Wolfgang C. Poller, MD, University Hospital Benjamin Franklin, Freie Universität, D-12200 Berlin, Germany. E-mail 100270.2245{at}compuserve.com
Background— The coxsackievirus and adenovirus receptor (CAR) was identified as a common cellular receptor for both viruses, but its biological and pathogenic relevance is uncertain. Knowledge of CAR localization in the human cardiovascular system is limited but important with respect to CAR-dependent viral infections and gene transfer using CAR-dependent viral vectors.
Methods and Results— Explanted failing hearts from 13 patients (8 with dilated cardiomyopathy [DCM] and 5 with other heart diseases [non-DCM]) and normal donor hearts (n=7) were investigated for the expression levels and subcellular localization of CAR and the adenovirus coreceptors 
vß3 and vß5 integrins. CAR immunoreactivity was very low in normal and non-DCM hearts, whereas strong CAR signals occurred at the intercalated discs and sarcolemma in 5 of the 8 DCM hearts (62.5%); these strong signals colocalized with both integrins. In all hearts, CAR was detectable in subendothelial layers of the vessel wall, but not on the luminal endothelial surface, and on interstitial cells. Human CAR (hCAR) expressed in rat cardiomyocytes was targeted to cell-cell contacts, which resembled CAR localization in DCM hearts and resulted in 15-fold increased adenovirus uptake.
Conclusions— Low hCAR abundance may render normal human myocardium resistant to CAR-dependent viruses, whereas re-expression of hCAR, such as that observed in DCM, may be a key determinant of cardiac susceptibility to viral infections. Asymmetric expression of hCAR in the vessel wall may be an important determinant of adenovirus tropism in humans. hCAR subcellular localization in human myocardium and hCAR targeting to cell-cell contacts in cardiomyocyte cultures suggest that hCAR may play a role in cell-cell contact formation.
Key Words: coxsackievirus • receptors, virus • gene therapy • cardiomyopathy • adenovirus
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