Department of Genetics, Istanbul University, Aziz Sancar Institute for Experimental Medicine, Istanbul, Turkey.
Graduate School of Health Sciences, Istanbul University, Istanbul, Turkey.
Mol Biol Rep. 2022 Aug;49(8):7677-7686. doi: 10.1007/s11033-022-07583-y. Epub 2022 May 27.
Cardiovascular diseases are the leading cause of death worldwide, with several conditions being affected by oxidative stress. Ferroptosis, recently identified programmed cell death mechanism, is relies on oxidative stress. This study aimed to determine the expressions of the genes involved in the molecular pathways of oxidative stress and ferroptosis and the association of these genes with CAD risk factors in CAD and non-CAD individuals.
The blood samples of individuals who underwent coronary angiography were collected and divided according to CAD status. Total RNA isolation was performed using the PAXgene RNA isolation kit from the whole blood samples. The mRNA expression levels of RTN3, GPX4, CAT, HMOX1, ELOVL5, SLC25A1, SLC7A11, and ACSL4 genes were determined using Real-Time PCR. Biochemical analyses were done before coronary angiography, and the results were evaluated statistically. The expression levels of the CAT gene are significantly lower in the CAD group when compared to non-CAD. HMOX1 expression levels are positively correlated with stenosis percentage, Gensini, and SYNTAX scores in the CAD group. RTN3, SLC25A1, and GPX4 mRNA expressions are correlated with HDL-C levels. Moreover, HbA1c levels and BMI, correlate negatively with ACSL4 expression in non-CAD controls. Also, ELOVL5 expression is negatively correlated with total bilirubin and direct bilirubin levels in the CAD group.
In this study, the genes related to oxidative stress and ferroptosis were found associated with biochemical parameters associated with CAD risk. These preliminary results may provide a new perspective to further studies investigating the reasons behind the identified associations.
心血管疾病是全球范围内的主要死因,其中有几种疾病受到氧化应激的影响。铁死亡是最近发现的程序性细胞死亡机制,依赖于氧化应激。本研究旨在确定参与氧化应激和铁死亡分子途径的基因的表达,并确定这些基因与 CAD 风险因素与 CAD 和非 CAD 个体的相关性。
收集接受冠状动脉造影的个体的血液样本,并根据 CAD 状况进行分组。使用 PAXgene RNA 分离试剂盒从全血样本中提取总 RNA。使用 Real-Time PCR 测定 RTN3、GPX4、CAT、HMOX1、ELOVL5、SLC25A1、SLC7A11 和 ACSL4 基因的 mRNA 表达水平。在冠状动脉造影前进行生化分析,并进行统计学评估。与非 CAD 组相比,CAD 组中的 CAT 基因表达水平显著降低。HMOX1 表达水平与 CAD 组的狭窄百分比、Gensini 和 SYNTAX 评分呈正相关。RTN3、SLC25A1 和 GPX4 mRNA 表达与 HDL-C 水平相关。此外,非 CAD 对照组中 HbA1c 水平和 BMI 与 ACSL4 表达呈负相关。此外,ELOVL5 表达与 CAD 组的总胆红素和直接胆红素水平呈负相关。
在这项研究中,与氧化应激和铁死亡相关的基因与与 CAD 风险相关的生化参数相关。这些初步结果可能为进一步研究确定的相关性背后的原因提供新的视角。