Secreted Frizzled Protein 3 Is A Novel Cardioprotective Mechanism Unique to the Clinically Relevant 4th Window of Ischemic Preconditioning.

Secreted Frizzled Protein 3 Is A Novel Cardioprotective Mechanism Unique to the Clinically Relevant 4th Window of Ischemic Preconditioning. Am J Physiol Heart Circ Physiol. 2020 Dec 18;: Authors: Vatner DE, Zhang J, Zhao X, Kudej RK, Yan L, Vatner SF Abstract Most studies on ischemic preconditioning (IPC) use one or two ischemic stimuli, before examining cardioprotection. In order to better simulate the clinical situation, we examined, in pigs, the effects of 6 episodes of 10 min coronary artery occlusion (CAO) 12 hours apart, followed by 60 min CAO. We named this model the 4th window of IPC. In order to determine the novel mechanisms mediating cardioprotection in the 4th window, gene analysis was examined in 4th window IPC cardiac tissue, 60 min after the last episode of 10 min CAO. Secreted Frizzled Related Protein 3 (sFRP3) was the most significantly upregulated gene that was unique to the 4th window, i.e., not found in the 1st, 2nd or 3rd window IPC. To study the effects of sFRP3 on cardioprotection, sFRP3 was injected in the hearts of WT mice. In the CAO/CAR model (30 min CAO followed by 24 hour CAR), infarct size was less, p<0.01, after sFRP3 injection (14±1.7%) compared to vehicle injection (48±1.6%). sFRP3 injection also protected the development of heart failure following permanent CAO for 2 wks. Left ventricular ejection fraction was significantly improved, p<0.05, at 2 weeks after CAO with sFRP3 (53±5%) compared w...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research