TY - JOUR
T1 - Nuclear Osteopontin Is a Marker of Advanced Heart Failure and Cardiac Allograft Vasculopathy
T2 - Evidence From Transplant and Retransplant Hearts
AU - Irion, Camila Iansen
AU - Dunkley, Julian C.
AU - John-Williams, Krista
AU - Condor Capcha, José Manuel
AU - Shehadeh, Serene A.
AU - Pinto, Andre
AU - Loebe, Matthias
AU - Webster, Keith A.
AU - Brozzi, Nicolas A.
AU - Shehadeh, Lina A.
N1 - Funding Information:
The authors would like to acknowledge Renzo Cifuentes, M.D., for his contribution to data acquisition. Funding. This work was supported by the following grants: grants from the National Institute of Health (1R01HL140468) and the Miami Heart Research Institute to LS, a grant from the NIH Diversity Supplement Award (3R01HL140468-02S1) to JD, and a grant 1S10OD023579-01 from the NIH for the VS120 Slide Scanner housed at the Miller School of Medicine Analytical Imaging Core Facility, University of Miami. The authors have nothing to disclose.
Publisher Copyright:
© Copyright © 2020 Irion, Dunkley, John-Williams, Condor Capcha, Shehadeh, Pinto, Loebe, Webster, Brozzi and Shehadeh.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8/13
Y1 - 2020/8/13
N2 - Background: Heart transplant is the gold standard therapy for patients with advanced heart failure. Over 5,500 heart transplants are performed every year worldwide. Cardiac allograft vasculopathy (CAV) is a common complication post-heart transplant which reduces survival and often necessitates heart retransplantation. Post-transplant follow-up requires serial coronary angiography and endomyocardial biopsy (EMB) for CAV and allograft rejection screening, respectively; both of which are invasive procedures. This study aims to determine whether osteopontin (OPN) protein, a fibrosis marker often present in chronic heart disease, represents a novel biomarker for CAV. Methods: Expression of OPN was analyzed in cardiac tissue obtained from patients undergoing heart retransplantation using immunofluorescence imaging (n = 20). Tissues from native explanted hearts and three serial follow-up EMB samples of transplanted hearts were also analyzed in five of these patients. Results: Fifteen out of 20 patients undergoing retransplantation had CAV. 13/15 patients with CAV expressed nuclear OPN. 5/5 patients with multiple tissue samples expressed nuclear OPN in both 1st and 2nd explanted hearts, while 0/5 expressed nuclear OPN in any of the follow-up EMBs. 4/5 of these patients had an initial diagnosis of dilated cardiomyopathy (DCM). Conclusion: Nuclear localization of OPN in cardiomyocytes of patients with CAV was evident at the time of cardiac retransplant as well as in patients with DCM at the time of the 1st transplant. The results implicate nuclear OPN as a novel biomarker for severe CAV and DCM.
AB - Background: Heart transplant is the gold standard therapy for patients with advanced heart failure. Over 5,500 heart transplants are performed every year worldwide. Cardiac allograft vasculopathy (CAV) is a common complication post-heart transplant which reduces survival and often necessitates heart retransplantation. Post-transplant follow-up requires serial coronary angiography and endomyocardial biopsy (EMB) for CAV and allograft rejection screening, respectively; both of which are invasive procedures. This study aims to determine whether osteopontin (OPN) protein, a fibrosis marker often present in chronic heart disease, represents a novel biomarker for CAV. Methods: Expression of OPN was analyzed in cardiac tissue obtained from patients undergoing heart retransplantation using immunofluorescence imaging (n = 20). Tissues from native explanted hearts and three serial follow-up EMB samples of transplanted hearts were also analyzed in five of these patients. Results: Fifteen out of 20 patients undergoing retransplantation had CAV. 13/15 patients with CAV expressed nuclear OPN. 5/5 patients with multiple tissue samples expressed nuclear OPN in both 1st and 2nd explanted hearts, while 0/5 expressed nuclear OPN in any of the follow-up EMBs. 4/5 of these patients had an initial diagnosis of dilated cardiomyopathy (DCM). Conclusion: Nuclear localization of OPN in cardiomyocytes of patients with CAV was evident at the time of cardiac retransplant as well as in patients with DCM at the time of the 1st transplant. The results implicate nuclear OPN as a novel biomarker for severe CAV and DCM.
KW - cardiac allograft vasculopathy
KW - dilated cardiomyopathy
KW - endomyocardial biopsy
KW - heart retransplantation
KW - heart transplant
KW - osteopontin
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U2 - 10.3389/fphys.2020.00928
DO - 10.3389/fphys.2020.00928
M3 - Article
AN - SCOPUS:85089915456
VL - 11
JO - Frontiers in Physiology
JF - Frontiers in Physiology
SN - 1664-042X
M1 - 928
ER -