Egr-1 functions as a master switch regulator of remote ischemic preconditioning-induced cardioprotection.

Despite improved treatment options myocardial infarction (MI) is still a leading cause of mortality and morbidity worldwide. Remote ischemic preconditioning (RIPC) is a mechanistic process that reduces myocardial infarction size and protects against ischemia reperfusion (I/R) injury. The zinc finger transcription factor early growth response-1 (Egr-1) is integral to the biological response to I/R, as its upregulation mediates the increased expression of inflammatory and prothrombotic processes. We aimed to determine the association and/or role of Egr-1 expression with the molecular mechanisms controlling the cardioprotective effects of RIPC. This study used H9C2 cells in vitro and a rat model of cardiac ischemia reperfusion (I/R) injury. We silenced Egr-1 with DNAzyme (ED5) in vitro and in vivo, before three cycles of RIPC consisting of alternating 5 min hypoxia and normoxia in cells or hind-limb ligation and release in the rat, followed by hypoxic challenge in vitro and I/R injury in vivo. Post-procedure, ED5 administration led to a significant increase in infarct size compared to controls (65.90 ± 2.38% vs. 41.00 ± 2.83%, p < 0.0001) following administration prior to RIPC in vivo, concurrent with decreased plasma IL-6 levels (118.30 ± 4.30 pg/ml vs. 130.50 ± 1.29 pg/ml, p < 0.05), downregulation of the cardioprotective JAK-STAT pathway, and elevated myocardial endothelial dysfunction. In vitro, ED5 administration abrogated IL-6 mRNA expression in H9C2 cells subjected to RIPC (0.95 ± 0.20 vs. 6.08 ± 1.40-fold relative to the control group, p < 0.05), resulting in increase in apoptosis (4.76 ± 0.70% vs. 2.23 ± 0.34%, p < 0.05) and loss of mitochondrial membrane potential (0.57 ± 0.11% vs. 1.0 ± 0.14%-fold relative to control, p < 0.05) in recipient cells receiving preconditioned media from the DNAzyme treated donor cells. This study suggests that Egr-1 functions as a master regulator of remote preconditioning inducing a protective effect against myocardial I/R injury through IL-6-dependent JAK-STAT signaling.

Comparison of two dimensional quantitative coronary angiography (2D-QCA) with optical coherence tomography (OCT) in the assessment of coronary artery lesion dimensions.

OBJECTIVES: There is limited data on how well 2D-QCA and OCT agree with each other for measurement of coronary artery lumen dimensions. We aimed to assess the agreement between the two modalities. METHODS: Patients undergoing OCT for assessment of coronary artery lesions were reviewed. Minimum luminal diameter (MLD), proximal reference diameter and distal reference diameter were measured for each lesion prior to stenting. RESULTS: OCT was performed in 64 patients and 40 lesions were suitable for analysis. There was a good correlation for proximal and distal reference diameters (r = 0.86, p < 0.0001 and r = 0.92, p < 0.0001 respectively). There was good agreement on Bland-Altman analysis; the proximal and distal reference diameters measured by QCA were on average 0.09 mm (95% CI, - 0.52 to 0.53 mm) and 0.1 mm (95% CI, - 0.59 to 0.6 mm) smaller than OCT respectively. There was a satisfactory correlation (r = 0.63, p = < 0.0001) between QCA and OCT for MLD. However, the MLD by QCA was 0.49 mm (95% CI, - 1.57 to 0.59 mm) smaller than OCT, suggesting a poor agreement for MLD. CONCLUSIONS: There is a good correlation and agreement between QCA and OCT for measurement of proximal and distal reference diameters. However, the MLD was underestimated by QCA.