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. Author manuscript; available in PMC: 2022 Nov 7.
Published in final edited form as: Science. 2022 Aug 4;377(6606):621–629. doi: 10.1126/science.abm1638

Figure 2: GPR35 mediates KynA ischemic protection.

Figure 2:

(A) Myocardial infarct size after in vivo cardiac ischemia/reperfusion (I/R) injury in wild-type and GPR35−/− mice. Where indicated mice were given 5 mg/kg KynA, 5 mg/kg pamoic acid, 50 mg/kg FG-4592, 5 mg/kg quinolinic acid, or vehicle by intraperitoneal injection 2 hours (or 24 hours where indicated) prior to ischemia. N=5 per group. (B) LVEDP in Langendorff assays after global I/R injury in wild-type and GPR35−/− mice. Where indicated the hearts were infused with 500 nM KynA, 100 μM FG-4592, or 500 nM quinolinic acid, or vehicle for 10 minutes (or 30 minute where indicated) prior to ischemia. N=4 per group. (C) Immunoblot analysis of lysates from Langendorff hearts perfused with 100 μM FG-4592 for the indicated times. (D) Myocardial infarct size after in vivo cardiac ischemia/reperfusion (I/R) injury in wild-type mice treated with 5 mg/kg KynA, 10 μg/kg pertussis toxin (PTX), both, or vehicle by intraperitoneal injection. Animals were treated with KynA or vehicle 2 hours before the onset of ischemia, while PTX was treated 24 hours prior to ischemia. N=4 per group (E) Myocardial infarct size after in vivo cardiac ischemia/reperfusion (I/R) injury in wild-type mice given GPR35 agonists. Where indicated, mice were given 5 mg/kg KynA, 5 mg/kg lodoxamide, 5 mg/kg zaprinast, 5 mg/kg quinolinic Acid, or vehicle by intraperitoneal injection 2 hours before the onset of ischemia. N=4 per group. (F) LVEDP in Langendorff assays after global I/R injury. Where indicated the hearts were infused with 500 nM KynA, 1 μM lodoxamide, 1 μM zaprinast, 500 nM quinolinic acid or vehicle for 10 minutes prior to ischemia. N=4 per group (G) Immunoblot of wild-type or GPR35−/− human IPS-derived cardiomyocytes stably expressing wild-type or R151A GPR35. (H) Fractional survival after simulated I/R injury ex vivo of human IPS-derived cardiomyocytes modified as in (G). Cell were pretreated with 20 μM KynA, 20 μM quinolinic acid, or DMSO for 1 hr prior to I/R. Shown are mean −/+SD. * indicates P value <0.05.