TY - JOUR
T1 - The cardioprotective effects of (-)-Epicatechin are mediated through arginase activity inhibition in a murine model of ischemia/reperfusion
AU - Ortiz-Vilchis, Pilar
AU - Ortiz-Flores, Miguel
AU - Pacheco, Marcela
AU - Ramirez-Sanchez, Israel
AU - Moreno-Ulloa, Aldo
AU - Vega, Lourdes
AU - Ortiz, Alicia
AU - Villarreal, Francisco
AU - Rubio-Gayosso, Ivan
AU - Najera, Nayelli
AU - Meaney, Eduardo
AU - Ceballos, Guillermo
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2018/1/5
Y1 - 2018/1/5
N2 - The production of nitric oxide (NO) by nitric oxide synthases (NOS) depends on the bioavailability of L-arginine as NOS competes with arginase for this common substrate. As arginase activity increases, less NO is produced and adverse cardiovascular consequences can emerge. (-)-Epicatechin (EPI), the most abundant flavonoid in cacao, has been reported to stimulate endothelial and neuronal NOS expression and function leading to enhanced vascular function and cardioprotective effects. However, little is known about the effects of EPI on myocardial arginase activity. The aim of the present study was to determine if EPI is able to interact and modulate myocardial arginase and NOS expression and activity. For this purpose, in silico modeling, in vitro activity assays and a rat model of ischemia/reperfusion injury were used. In silico and in vitro results demonstrate that EPI can interact with arginase and significantly decrease its activity. In vivo, 10 days of EPI pretreatment reduces ischemic myocardium arginase expression while increasing NOS expression and phosphorylation levels. Altogether, these results may partially account for the cardioprotective effects of EPI.
AB - The production of nitric oxide (NO) by nitric oxide synthases (NOS) depends on the bioavailability of L-arginine as NOS competes with arginase for this common substrate. As arginase activity increases, less NO is produced and adverse cardiovascular consequences can emerge. (-)-Epicatechin (EPI), the most abundant flavonoid in cacao, has been reported to stimulate endothelial and neuronal NOS expression and function leading to enhanced vascular function and cardioprotective effects. However, little is known about the effects of EPI on myocardial arginase activity. The aim of the present study was to determine if EPI is able to interact and modulate myocardial arginase and NOS expression and activity. For this purpose, in silico modeling, in vitro activity assays and a rat model of ischemia/reperfusion injury were used. In silico and in vitro results demonstrate that EPI can interact with arginase and significantly decrease its activity. In vivo, 10 days of EPI pretreatment reduces ischemic myocardium arginase expression while increasing NOS expression and phosphorylation levels. Altogether, these results may partially account for the cardioprotective effects of EPI.
KW - Arginase
KW - Epicatechin
KW - Ischemia/reperfusion injury
KW - Nitric oxide synthase
UR - http://www.scopus.com/inward/record.url?scp=85033406625&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2017.11.007
DO - 10.1016/j.ejphar.2017.11.007
M3 - Artículo
C2 - 29126791
SN - 0014-2999
VL - 818
SP - 335
EP - 342
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -