Quantitative RT-PCR assays of hypoxia-inducible factor-1alpha, erythropoietin and vascular endothelial growth factor mRNA transcripts in the kidneys with regard to the cause of death in medicolegal autopsy

Abstract

Accumulating studies demonstrate that the expressions of hypoxia-inducible factor 1 (HIF-1), erythropoietin (EPO) and vascular endothelial growth factor (VEGF) depend on cellular oxygen tension, which is involved in the pathological process of tissue hypoxia and/or ischemia. The present study investigated hypoxia-inducible factor-1alpha (HIF-1alpha), EPO and VEGF mRNA expressions in the kidney with regard to the cause of death in medicolegal autopsy. Relative quantifications of HIF-1alpha, EPO and VEGF mRNAs, based on real-time TaqMan reverse transcription-polymerase chain reaction (RT-PCR), were performed on tissue specimens obtained from consistent sites of the bilateral renal cortices. The cases (total, n=245, 6-48h postmortem) included fatal blunt/sharp instrument injuries (n=53/31), asphyxia (n=28: aspiration, n=8; strangulation/hanging, n=20), drowning (n=27), fire fatality (n=62), acute myocardial infarction/ischemia (AMI, n=39), and gastrointestinal hemorrhage (n=5). Both HIF-1alpha and EPO mRNA levels were significantly lower in drowning cases. More characteristic findings were found for VEGF mRNA: it showed higher expression levels for AMI, acute blunt/sharp instrument injury, and aspiration, whereas it was lower for neck compression (strangulation/hanging), drowning, fire fatality with higher blood carboxyhemoglobin (COHb) levels (>60%), peracute blunt injury, and gastrointestinal hemorrhage. Quantitative assays of renal HIF-1alpha, EPO and VEGF mRNA transcripts are potentially useful for investigating the pathophysiology of death, and VEGF mRNA may be especially useful as an indication of acute circulatory failure.