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Dilated cardiomyopathy alters the expression patterns of CAR and other adenoviral receptors in human heart




TekijätToivonen R, Mayranpaa MI, Kovanen PT, Savontaus M

KustantajaSPRINGER

Julkaisuvuosi2010

JournalHistochemistry and Cell Biology

Tietokannassa oleva lehden nimiHISTOCHEMISTRY AND CELL BIOLOGY

Lehden akronyymiHISTOCHEM CELL BIOL

Numero sarjassa3

Vuosikerta133

Numero3

Aloitussivu349

Lopetussivu357

Sivujen määrä9

ISSN0948-6143

DOIhttps://doi.org/10.1007/s00418-009-0666-1


Tiivistelmä

Gene therapy trials for heart failure have demonstrated the key role of efficient gene transfer in achieving therapeutic efficacy. An attractive approach to improve adenoviral gene transfer is to use alternative virus serotypes with modified tropism. We performed a detailed analysis of cardiac expression of receptors for several adenovirus serotypes with a focus on differential expression of CAR and CD46, as adenoviruses targeting these receptors have been used in various applications. Explanted hearts from patients with DCM and healthy donors were analyzed using Q-RT-PCR, western blot and immunohistochemistry. Q-RT-PCR and Western analyses revealed robust expression of all receptors except CD80 in normal hearts with lower expression levels in DCM. Immunohistochemical analyses demonstrated that CD46 expression was somewhat higher than CAR both in normal and DCM hearts with highest levels of expression in intramyocardial coronary vessels. Total CAR expression was upregulated in DCM. Triple staining on these vessels demonstrated that both CAR and CD46 were confined to the subendothelial layer in normal hearts. The situation was clearly different in DCM, where both CAR and CD46 were expressed by endothelial cells. The induction of expression of CAR and CD46 by endothelial cells in DCM suggests that viruses targeting these receptors could more easily gain entry to heart cells after intravascular administration. This finding thus has potential implications for the development of targeted gene therapy for heart failure.




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