Biochemical Investigation of the Association of Apolipoprotein E Gene Allele Variations with Insulin Resistance and Amyloid-β Aggregation in Cardiovascular Disease

IF 2.9 4区 医学 Q2 Medicine
Komal Jabeen, Kanwal Rehman, Muhammad Sajid Hamid Akash, Amjad Hussain, Mudassar Shahid, Bushra Sadaf
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Abstract

This article investigates the intricate associations between apolipoprotein E (APOE) gene alleles variation, insulin resistance (IR) and amyloid-β aggregation in cardiovascular disease (CVD) patients. A cohort of 250 patients exhibiting the symptoms of CVD and 50 control subjects participated in this study. After applying the stringent inclusion and exclusion criteria, the diseased group was further stratified into three categories: CVD+ (Alzheimer's disease) AD, CVD + (diabetes mellitus) DM and CVD + DM + AD. Blood samples were collected from all recruited participants for the biochemical analyses of lipid profile, glycaemic status, liver function enzymes, inflammatory and oxidative stress biomarkers. Tetra amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) was employed for APOE gene analysis. Biochemical evaluations revealed the significant elevations in the serum levels of glucose, liver enzymes, interleukin-6 (IL-6), cholesterol, low-density lipoproteins (LDL), triglycerides (TG) and malondialdehyde (MDA) in CVD + DM + AD group. Conversely, the serum levels of insulin, HDL and hexokinase decreased in CVD + DM + AD group compared to the controls and other CVD groups. Tetra ARMS-PCR results indicated a higher percentage of the risk allele in CVD + DM + AD group when compared with the other groups. Our study elucidates the multifaceted cardiovascular risk factors contributing to IR and AD in CVD patients. Age-related risk factors, prevalence of APOE risk alleles and the impact of statin use on AD incidences were identified. These findings underscore the need for tailored preventive measures, particularly in APOEε4 and ε3/ε4 carriers with CVD. Further studies should delve into the knowledge-based protocols to comprehend the underlying mechanisms. Focusing on the therapeutic targets to prevent or delay DM and AD progression in CVDs, especially in APOEε4 carriers, is essential.

Abstract Image

载脂蛋白 E 基因等位基因变异与心血管疾病中胰岛素抵抗和淀粉样蛋白-β聚集关系的生化研究
本文研究了心血管疾病(CVD)患者体内载脂蛋白E(APOE)基因等位基因变异、胰岛素抵抗(IR)和淀粉样蛋白-β聚集之间错综复杂的关系。250名有心血管疾病症状的患者和50名对照组受试者参加了这项研究。在采用严格的纳入和排除标准后,患病群体被进一步分为三类:心血管疾病+(阿尔茨海默病)AD、心血管疾病+(糖尿病)DM 和心血管疾病+DM+AD。研究人员采集了所有受试者的血液样本,用于脂质概况、血糖状况、肝功能酶、炎症和氧化应激生物标志物的生化分析。APOE 基因分析采用了四扩增-难辨突变系统聚合酶链反应(ARMS-PCR)。生化评估显示,CVD + DM + AD 组血清中葡萄糖、肝酶、白细胞介素-6(IL-6)、胆固醇、低密度脂蛋白(LDL)、甘油三酯(TG)和丙二醛(MDA)水平显著升高。相反,与对照组和其他心血管疾病组相比,CVD + DM + AD 组血清中的胰岛素、高密度脂蛋白和己糖激酶水平有所下降。Tetra ARMS-PCR 结果显示,与其他组别相比,CVD + DM + AD 组的风险等位基因比例更高。我们的研究阐明了导致心血管疾病患者出现 IR 和 AD 的多方面心血管风险因素。研究还发现了与年龄相关的风险因素、APOE风险等位基因的患病率以及他汀类药物的使用对AD发病率的影响。这些发现强调了采取有针对性的预防措施的必要性,尤其是对患有心血管疾病的APOEε4和ε3/ε4携带者。进一步的研究应深入探讨基于知识的方案,以了解其潜在机制。重点研究预防或延缓心血管疾病(尤其是 APOEε4 携带者)中的 DM 和 AD 进展的治疗靶点至关重要。
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来源期刊
CiteScore
6.20
自引率
0.00%
发文量
128
审稿时长
6 months
期刊介绍: Clinical and Experimental Pharmacology and Physiology is an international journal founded in 1974 by Mike Rand, Austin Doyle, John Coghlan and Paul Korner. Our focus is new frontiers in physiology and pharmacology, emphasizing the translation of basic research to clinical practice. We publish original articles, invited reviews and our exciting, cutting-edge Frontiers-in-Research series’.
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