TY - JOUR
T1 - Acute administration of the olive constituent, oleuropein, combined with ischemic postconditioning increases myocardial protection by modulating oxidative defense
AU - Tsoumani, Maria
AU - Georgoulis, Anastasios
AU - Nikolaou, Panagiota Efstathia
AU - Kostopoulos, Ioannis V.
AU - Dermintzoglou, Theano
AU - Papatheodorou, Ioanna
AU - Zoga, Anastasia
AU - Efentakis, Panagiotis
AU - Konstantinou, Maria
AU - Gikas, Evangelos
AU - Kostomitsopoulos, Nikolaos
AU - Papapetropoulos, Andreas
AU - Lazou, Antigone
AU - Skaltsounis, Alexios Leandros
AU - Hausenloy, Derek J.
AU - Tsitsilonis, Ourania
AU - Tseti, Ioulia
AU - Di Lisa, Fabio
AU - Iliodromitis, Efstathios K.
AU - Andreadou, Ioanna
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/4
Y1 - 2021/4
N2 - Oleuropein, one of the main polyphenolic constituents of olive, is cardioprotective against ischemia reperfusion injury (IRI). We aimed to assess the cardioprotection afforded by acute administration of oleuropein and to evaluate the underlying mechanism. Importantly, since antioxidant therapies have yielded inconclusive results in attenuating IRI-induced damage on top of conditioning strategies, we investigated whether oleuropein could enhance or imbed the cardioprotective manifestation of ischemic postconditioning (PostC). Oleuropein, given during ischemia as a single intravenous bolus dose reduced the infarct size compared to the control group both in rabbits and mice subjected to myocardial IRI. None of the inhibitors of the cardioprotective pathways, L-NAME, wortmannin and AG490, influence its infarct size limiting effects. Combined oleuropein and PostC cause further limitation of infarct size in comparison with PostC alone in both animal models. Oleuropein did not inhibit the calcium induced mitochondrial permeability transition pore opening in isolated mitochondria and did not increase cGMP production. To provide further insights to the different cardioprotective mechanism of oleuropein, we sought to characterize its anti-inflammatory potential in vivo. Oleuropein, PostC and their combination reduce inflammatory monocytes infiltration into the heart and the circulating monocyte cell population. Oleuropein's mechanism of action involves a direct protective effect on cardiomyocytes since it significantly increased their viability following simulated IRI as compared to non-treated cells. Οleuropein confers additive cardioprotection on top of PostC, via increasing the expression of the transcription factor Nrf-2 and its downstream targets in vivo. In conclusion, acute oleuropein administration during ischemia in combination with PostC provides robust and synergistic cardioprotection in experimental models of IRI by inducing antioxidant defense genes through Nrf-2 axis and independently of the classic cardioprotective signaling pathways (RISK, cGMP/PKG, SAFE).
AB - Oleuropein, one of the main polyphenolic constituents of olive, is cardioprotective against ischemia reperfusion injury (IRI). We aimed to assess the cardioprotection afforded by acute administration of oleuropein and to evaluate the underlying mechanism. Importantly, since antioxidant therapies have yielded inconclusive results in attenuating IRI-induced damage on top of conditioning strategies, we investigated whether oleuropein could enhance or imbed the cardioprotective manifestation of ischemic postconditioning (PostC). Oleuropein, given during ischemia as a single intravenous bolus dose reduced the infarct size compared to the control group both in rabbits and mice subjected to myocardial IRI. None of the inhibitors of the cardioprotective pathways, L-NAME, wortmannin and AG490, influence its infarct size limiting effects. Combined oleuropein and PostC cause further limitation of infarct size in comparison with PostC alone in both animal models. Oleuropein did not inhibit the calcium induced mitochondrial permeability transition pore opening in isolated mitochondria and did not increase cGMP production. To provide further insights to the different cardioprotective mechanism of oleuropein, we sought to characterize its anti-inflammatory potential in vivo. Oleuropein, PostC and their combination reduce inflammatory monocytes infiltration into the heart and the circulating monocyte cell population. Oleuropein's mechanism of action involves a direct protective effect on cardiomyocytes since it significantly increased their viability following simulated IRI as compared to non-treated cells. Οleuropein confers additive cardioprotection on top of PostC, via increasing the expression of the transcription factor Nrf-2 and its downstream targets in vivo. In conclusion, acute oleuropein administration during ischemia in combination with PostC provides robust and synergistic cardioprotection in experimental models of IRI by inducing antioxidant defense genes through Nrf-2 axis and independently of the classic cardioprotective signaling pathways (RISK, cGMP/PKG, SAFE).
KW - Antioxidant defense systems
KW - Cardioprotection
KW - Inflammation
KW - Ischemia-reperfusion injury
KW - Oleuropein
KW - Postconditioning
UR - http://www.scopus.com/inward/record.url?scp=85103131467&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103131467&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2021.02.011
DO - 10.1016/j.freeradbiomed.2021.02.011
M3 - Article
C2 - 33582227
AN - SCOPUS:85103131467
SN - 0891-5849
VL - 166
SP - 18
EP - 32
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -