TY - JOUR
T1 - Accumulation of 5-oxoproline in myocardial dysfunction and the protective effects of OPLAH
AU - Van Der Pol, Atze
AU - Gil, Andres
AU - Silljé, Herman H.W.
AU - Tromp, Jasper
AU - Ovchinnikova, Ekaterina S.
AU - Vreeswijk-Baudoin, Inge
AU - Hoes, Martijn
AU - Domian, Ibrahim J.
AU - Van De Sluis, Bart
AU - Van Deursen, Jan M.
AU - Voors, Adriaan A.
AU - Van Veldhuisen, Dirk J.
AU - Van Gilst, Wiek H.
AU - Berezikov, Eugene
AU - Van Der Harst, Pim
AU - De Boer, Rudolf A.
AU - Bischoff, Rainer
AU - Van Der Meer, Peter
N1 - Publisher Copyright:
© 2017 The Authors.
PY - 2017/11/8
Y1 - 2017/11/8
N2 - In response to heart failure (HF), the heart reacts by repressing adult genes and expressing fetal genes, thereby returning to a more fetal-like gene profile. To identify genes involved in this process, we carried out transcriptional analysis on murine hearts at different stages of development and on hearts from adult mice with HF. Our screen identified Oplah, encoding for 5-oxoprolinase, amember of the g-glutamyl cycle that functions by scavenging 5-oxoproline. OPLAH depletion occurred as a result of cardiac injury, leading to elevated 5-oxoproline and oxidative stress, whereas OPLAH overexpression improved cardiac function after ischemic injury. In HF patients, we observed elevated plasma 5-oxoproline, which was associated with a worse clinical outcome. Understanding and modulating fetal-like genes in the failing heart may lead to potential diagnostic, prognostic, and therapeutic options in HF.
AB - In response to heart failure (HF), the heart reacts by repressing adult genes and expressing fetal genes, thereby returning to a more fetal-like gene profile. To identify genes involved in this process, we carried out transcriptional analysis on murine hearts at different stages of development and on hearts from adult mice with HF. Our screen identified Oplah, encoding for 5-oxoprolinase, amember of the g-glutamyl cycle that functions by scavenging 5-oxoproline. OPLAH depletion occurred as a result of cardiac injury, leading to elevated 5-oxoproline and oxidative stress, whereas OPLAH overexpression improved cardiac function after ischemic injury. In HF patients, we observed elevated plasma 5-oxoproline, which was associated with a worse clinical outcome. Understanding and modulating fetal-like genes in the failing heart may lead to potential diagnostic, prognostic, and therapeutic options in HF.
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U2 - 10.1126/scitranslmed.aam8574
DO - 10.1126/scitranslmed.aam8574
M3 - Article
C2 - 29118264
AN - SCOPUS:85033675098
SN - 1946-6234
VL - 9
JO - Science translational medicine
JF - Science translational medicine
IS - 415
M1 - 8574
ER -