Quantitative analysis of kruppel-like factor 5-related messenger RNA transcripts in ischemic myocardium for discrimination of death causes

Abstract

Background: Accumulated studies have demonstrated that Kruppel-like factor 5 (KLF5), a transcription factor, plays an important role in regulating cell proliferation and tissue remodeling through the expression of its downstream genes. KLF5-related factors are expected to be involved in the healing process after myocardial injury or myocardial ischemic changes, especially for the forensic diagnosis of myocardial ischemic physiopathology. Aim and Objectives: This study aimed to explore the discrimination ability and applicability of KLF5-related factors in SCD caused by MI compared with other causes of death to provide further insights into the forensic diagnosis of myocardial ischemic pathology. Materials and Methods: The relative quantification of F-Box and WD Repeat Domain Containing 7 (FBW7), KLF5, factor-binding protein (FGFBP) 1, and FGFBP2 messenger RNAs (mRNAs) in myocardial tissue samples was performed using real-time fluorescence quantitative reverse transcription polymerase chain reaction. KLF5 and FGFBP1/2 protein levels were examined using immunohistochemistry (IHC). The forensic autopsy cases (27 in total, autopsy within 72 h postmortem) included seven cases of acute myocardial infarction and 10 cases of acute myocardial ischemia. There were 10 cases in the control group, including four cases of traffic injury one case of injury by fall from height, one case of electric death, and four cases of blunt force injury. Results: Characteristic results were found in myocardial samples from three groups of deaths: KLF5 and FGFBP1 mRNA levels were significantly elevated in the infarction and ischemia groups, while FBW7 mRNA levels were significantly decreased. FBW7 is an important ubiquitin ligase that can mediate the degradation of KLF5 protein. In addition, FBW7 and FGFBP2 mRNA levels were decreased in the infarction group compared with the ischemia group. The IHC results were consistent with the observed mRNA expression patterns. Conclusions: Quantitative detection of FBW7, KLF5, FGFBP1, and FGFBP2 mRNA transcripts in myocardial tissues supports the pathophysiological study of myocardial ischemic diseases and provides molecular pathological evidence for forensic discrimination of death causes.

Keywords

• f-box and wd 40 repeat domain–containing 7
• fibroblast growth factor-binding protein
• kruppel-like factor 5
• myocardial ischemia