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射血分数降低的心力衰竭患者外周血淋巴细胞中的基因组不稳定

Genome instability in peripheral blood lymphocytes of patients with heart failure and reduced ejection fraction.

作者信息

Tubić Vukajlović Jovana, Simić Ivan, Smiljanić Zorica, Grujičić Darko, Milošević-Djordjević Olivera

机构信息

University of Kragujevac, Faculty of Science, Department of Biology and Ecology, 34000 Kragujevac, Serbia.

University of Kragujevac, Faculty of Medical Sciences, Department of Internal Medicine, 34000 Kragujevac, Serbia.

出版信息

Mutagenesis. 2023 May 12;38(2):84-92. doi: 10.1093/mutage/gead002.

Abstract

Heart failure (HF) is a complex clinical condition characterized by functional and structural defects of the myocardium, but genetic and environmental factors are considered to play an important role in the development of the disease. In the present study, we investigated the genome instability (DNA and chromosomal damage) in patients with heart failure with reduced ejection fraction (HFrEF) ≤40% and its association with risk factors. The studied population included 48 individuals, of which 29 HFrEF patients (mean age 57.41 ± 5.74 years) and 19 healthy controls (mean age 57.63 ± 6.09 years). The genetic damage index in peripheral blood lymphocytes was analyzed using the comet assay, while micronuclei frequency and nuclear division index were analyzed using the cytokinesis-block micronucleus assay. Our results showed that HFrEF patients had a significantly higher genetic damage index compared with the healthy controls (P < .001). Cytokinesis-block micronucleus assay showed that the average micronucleus frequency in peripheral blood lymphocytes of patients was significantly higher, while the nuclear division index values were significantly lower than in controls (P < .01). Using multiple linear regression analysis, pathological state, ejection fraction, creatinine, glucose, associated disease, residence, proBNP, troponin, urea, ACE-inhibitors, and length of the drug therapy were identified as predictors of DNA and/or chromosomal damage in HF patients. We can conclude that DNA and chromosomal damage was increased in patients with HF, which may be a consequence of disease and/or drug therapy.

摘要

心力衰竭(HF)是一种复杂的临床病症,其特征为心肌的功能和结构缺陷,但遗传和环境因素被认为在该疾病的发展中起重要作用。在本研究中,我们调查了射血分数降低(HFrEF)≤40%的心力衰竭患者的基因组不稳定性(DNA和染色体损伤)及其与危险因素的关联。研究人群包括48名个体,其中29名HFrEF患者(平均年龄57.41±5.74岁)和19名健康对照者(平均年龄57.63±6.09岁)。使用彗星试验分析外周血淋巴细胞中的遗传损伤指数,同时使用胞质分裂阻滞微核试验分析微核频率和核分裂指数。我们的结果表明,与健康对照者相比,HFrEF患者的遗传损伤指数显著更高(P<.001)。胞质分裂阻滞微核试验表明,患者外周血淋巴细胞中的平均微核频率显著更高,但核分裂指数值显著低于对照者(P<.01)。通过多元线性回归分析确定,病理状态、射血分数、肌酐、葡萄糖、相关疾病、居住地、脑钠肽前体、肌钙蛋白、尿素、血管紧张素转换酶抑制剂和药物治疗时长是HF患者DNA和/或染色体损伤的预测因素。我们可以得出结论,HF患者的DNA和染色体损伤增加,这可能是疾病和/或药物治疗的结果。

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