Paper Report for: Hanif_2016_Am.J.Physiol.Regul.Integr.Comp.Physiol_311_R676
Reference
Title: Deletion of soluble epoxide hydrolase enhances coronary reactive hyperemia in isolated mouse heart: role of oxylipins and PPARgamma Hanif A, Edin ML, Zeldin DC, Morisseau C, Nayeem MA Ref: American Journal of Physiology Regul Integr Comp Physiol, 311:R676, 2016 : PubMed
The relationship between soluble epoxide hydrolase (sEH) and coronary reactive hyperemia (CRH) response to a brief ischemic insult is not known. Epoxyeicosatrienoic acids (EETs) exert cardioprotective effects in ischemia/reperfusion injury. sEH converts EETs into dihydroxyeicosatrienoic-acids (DHETs). Therefore, we hypothesized that knocking out sEH enhances CRH through modulation of oxylipin profiles, including an increase in EET/DHET ratio. Compared with sEH+/+, sEH-/- mice showed enhanced CRH, including greater repayment volume (RV; 28% higher, P < 0.001) and repayment/debt ratio (32% higher, P < 0.001). Oxylipins from the heart perfusates were analyzed by LC-MS/MS. The 14,15-EET/14,15-DHET ratio was 3.7-fold higher at baseline (P < 0.001) and 5.6-fold higher post-ischemia (P < 0.001) in sEH-/- compared with sEH+/+ mice. Likewise, the baseline 9,10- and 12,13-EpOME/DiHOME ratios were 3.2-fold (P < 0.01) and 3.7-fold (P < 0.001) higher, respectively in sEH-/- compared with sEH+/+ mice. 13-HODE was also significantly increased at baseline by 71% (P < 0.01) in sEH-/- vs. sEH+/+ mice. Levels of 5-, 11-, 12-, and 15-hydroxyeicosatetraenoic acids were not significantly different between the two strains (P > 0.05), but were decreased postischemia in both groups (P = 0.02, P = 0.04, P = 0.05, P = 0.03, respectively). Modulation of CRH by peroxisome proliferator-activated receptor gamma (PPARgamma) was demonstrated using a PPARgamma-antagonist (T0070907), which reduced repayment volume by 25% in sEH+/+ (P < 0.001) and 33% in sEH-/- mice (P < 0.01), and a PPARgamma-agonist (rosiglitazone), which increased repayment volume by 37% in both sEH+/+ (P = 0.04) and sEH-/- mice (P = 0.04). l-NAME attenuated CRH in both sEH-/- and sEH+/+ These data demonstrate that genetic deletion of sEH resulted in an altered oxylipin profile, which may have led to an enhanced CRH response.
Hanif A, Edin ML, Zeldin DC, Morisseau C, Nayeem MA (2016) Deletion of soluble epoxide hydrolase enhances coronary reactive hyperemia in isolated mouse heart: role of oxylipins and PPARgamma American Journal of Physiology Regul Integr Comp Physiol311: R676-R688
Hanif A, Edin ML, Zeldin DC, Morisseau C, Nayeem MA (2016) American Journal of Physiology Regul Integr Comp Physiol311: R676-R688