Deletion of the EphA2 receptor exacerbates myocardial injury and the progression of ischemic cardiomyopathy

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dc.contributor.authorO'Neal, Wesley T.
dc.contributor.authorGriffin, William F.
dc.contributor.authorKent, Susan D.
dc.contributor.authorFaiz, Filza
dc.contributor.authorHodges, Jonathan
dc.contributor.authorVuncannon, Jackson
dc.contributor.authorVirag, Jitka A. I.
dc.date.accessioned2016-06-28T13:29:29Z
dc.date.available2016-06-28T13:29:29Z
dc.date.issued2014-04
dc.description.abstractEphrinA1-EphA-receptor signaling is protective during myocardial infarction (MI). The EphA2-receptor (EphA2-R) potentially mediates cardiomyocyte survival. To determine the role of the EphA2-R in acute non-reperfused myocardial injury in vivo, infarct size, inflammatory cell density, NF-κB, p-AKT/Akt, and MMP-2 protein levels, and changes in ephrinA1/EphA2-R gene expression profile were assessed 4 days post-MI in B6129 wild-type (WT) and EphA2-R-mutant (EphA2-R-M) mice lacking a functional EphA2-R. Fibrosis, capillary density, morphometry of left ventricular chamber and infarct dimensions, and cardiac function also were measured 4 weeks post-MI to determine the extent of ventricular remodeling. EphA2-R-M infarct size and area of residual necrosis were 31.7% and 113% greater than WT hearts, respectively. Neutrophil and macrophage infiltration were increased by 46% and 84% in EphA2-R-M hearts compared with WT, respectively. NF-κB protein expression was 1.9-fold greater in EphA2-R-M hearts at baseline and 56% less NF-κB after infarction compared with WT. EphA6 gene expression was 2.5-fold higher at baseline and increased 9.8-fold 4 days post-MI in EphA2-R-M hearts compared with WT. EphrinA1 gene expression in EphA2-R-M hearts was unchanged at baseline and decreased by 42% 4 days post-MI compared with WT hearts. EphA2-R-M hearts had 66.7% less expression of total Akt protein and 59% less p-Akt protein than WT hearts post-MI. EphA2-R-M hearts 4 weeks post-MI had increased chamber dilation and interstitial fibrosis and decreased MMP-2 expression and capillary density compared with WT. In conclusion, the EphA2-R is necessary to appropriately modulate the inflammatory response and severity of early injury during acute MI, thereby influencing the progression of ischemic cardiomyopathy.en_US
dc.identifier.citationFrontiers in Physiology; 5: p. 1-9en_US
dc.identifier.doi10.3389/fphys.2014.00132
dc.identifier.issn1664-042X
dc.identifier.pmidpmc4006041en_US
dc.identifier.urihttp://hdl.handle.net/10342/5793
dc.relation.urihttp://journal.frontiersin.org/article/10.3389/fphys.2014.00132/fullen_US
dc.titleDeletion of the EphA2 receptor exacerbates myocardial injury and the progression of ischemic cardiomyopathyen_US
dc.typeArticleen_US
ecu.journal.nameFrontiers in Physiologyen_US
ecu.journal.pages1-9en_US
ecu.journal.volume5en_US

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