Association between time to reperfusion and echocardiography assessed left ventricular filling pressure in patients with first ST-segment elevation myocardial infarction undergoing primary coronary intervention

  Background: Diastolic dysfunction and elevated left ventricular (LV) filling pressure fol­lowing acute myocardial infarction are associated with adverse outcomes. Although time to reperfusion is a powerful prognostic marker following acute myocardial infarction, little is known about its impact on diastolic function and LV filling pressure. We hypothesized that delayed time to reperfusion will be associated with worse diastolic function. Methods: This study included 180 consecutive patients with first ST elevation myocardial in­farction (STEMI) treated by primary percutaneous coronary intervention (PCI). They presen­ted of chest pain within 24 h and underwent echocardiography within 3 days of primary PCI. Results: Median time to reperfusion, defined as the time from symptom onset to reperfusion at the end of primary PCI, was 185 min (interquartile range 120–660). Patients with reperfu­sion time > 185 min (n = 92) had a significantly higher E/septal e’ (13.3 ± 5.0 vs. 9.7 ± 2.3, p < 0.001) and E/lateral e’ (9.8 ± 3.5 vs. 7.8 ± 2.2, p < 0.001) ratios, and more advanced diastolic grade (p < 0.001) compared to those having early reperfusion (n = 88). There were no significant differences in LV ejection fraction and left atrial volume between the two groups. Time to reperfusion was an independent predictor of early E/average e’ ratio. The adverse ef­fect of late reperfusion on diastolic dysfunction was more prominent in patients with anterior myocardial infarction. Conclusions: Longer time to reperfusion is associated with early elevated LV diastolic pres­sure in primary PCI-treated patients with STEMI.

Ectopic PDX-1 Expression Directly Reprograms Human Keratinocytes along Pancreatic Insulin-Producing Cells Fate

BACKGROUND: Cellular differentiation and lineage commitment have previously been considered irreversible processes. However, recent studies have indicated that differentiated adult cells can be reprogrammed to pluripotency and, in some cases, directly into alternate committed lineages. However, although pluripotent cells can be induced in numerous somatic cell sources, it was thought that inducing alternate committed lineages is primarily only possible in cells of developmentally related tissues. Here, we challenge this view and analyze whether direct adult cell reprogramming to alternate committed lineages can cross the boundaries of distinct developmental germ layers. METHODOLOGY/PRINCIPAL FINDINGS: We ectopically expressed non-integrating pancreatic differentiation factors in ectoderm-derived human keratinocytes to determine whether these factors could directly induce endoderm-derived pancreatic lineage and β-cell-like function. We found that PDX-1 and to a lesser extent other pancreatic transcription factors, could rapidly and specifically activate pancreatic lineage and β-cell-like functional characteristics in ectoderm-derived human keratinocytes. Human keratinocytes transdifferentiated along the β cell lineage produced processed and secreted insulin in response to elevated glucose concentrations. Using irreversible lineage tracing for KRT-5 promoter activity, we present supporting evidence that insulin-positive cells induced by ectopic PDX-1 expression are generated in ectoderm derived keratinocytes. CONCLUSIONS/SIGNIFICANCE: These findings constitute the first demonstration of human ectoderm cells to endoderm derived pancreatic cells transdifferentiation. The study represents a proof of concept which suggests that transcription factors induced reprogramming is wider and more general developmental process than initially considered. These results expanded the arsenal of adult cells that can be used as a cell source for generating functional endocrine pancreatic cells. Directly reprogramming somatic cells into alternate desired tissues has important implications in developing patient-specific, regenerative medicine approaches