Myocardial ischaemia/reperfusion-induced Ca2+ overload promotes cardiomyocyte death. Lysophosphatidolinositol (LPI), the endogenous ligand of GPR55 can increase [Ca2+]i which may contribute to apoptosis. Therefore LPI, through an action at GPR55 may contribute to myocardial ischaemia/reperfusion injury. Hearts from male/female wild-type (WT) and GPR55+/− mice (9–12 week old; 18–32g) were perfused in Langendorff mode and subjected to global ischaemia and reperfusion (each 30 minutes). Hearts from both strains were treated with vehicle (0.1% DMSO) or LPI (10 µM) pre-ischaemia or during early reperfusion. Infarct size was determined via 1% TTC staining and computerised planimetry. Data are expressed as mean±S.E.M. and were compared using a one-way ANOVA test followed by a ‘Bonferroni’ post-hoc test/‘Student's unpaired t-test’. In vehicle treated hearts, infarct size did not statistically differ between WT (n=14) and GPR55+/− (n=3) groups (33.9±2.9% vs. 42.6±1.9%, respectively). In the WT group, LPI administration pre-ischaemia (n=14) increased infarct size (48±4.7% vs. 33.9±2.9%; P<0.05), an effect which did not occur if LPI was administered post-ischaemia (n=9) (38.1±3.3% vs. 33.9±2.9%). Moreover, neither pre- (n=3) nor post-ischaemic (n=3) LPI administration to GPR55+/− hearts altered infarct size compared to controls (n=3) (43.7±4.7% vs. 42.6±1.9% and 49.9±9.6% vs. 42.6±1.9%, respectively). To investigate signalling mechanisms involved in LPI's detrimental effect, the ROCK inhibitor, Y-27632 dihydrochloride (10 and 50 µM; n=6 and 7, respectively) was administered to WT hearts pre-LPI challenge. At 10 µM, this inhibitor attenuated the deleterious effect of LPI (33.2±3.9% vs. 48.0±4.7%; P<0.05). In conclusion, administration of exogenous LPI pre-ischaemia exacerbates myocardial tissue injury via a GPR55-ROCK dependent mechanism.
- CARDIAC PROCEDURES AND THERAPY
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