Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan.
Department of Pharmacy, The Women University, Multan, Pakistan.
Clin Exp Pharmacol Physiol. 2025 Jan;52(1):e70007. doi: 10.1111/1440-1681.70007.
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.
这篇文章研究了载脂蛋白 E (APOE) 基因等位基因变异、胰岛素抵抗 (IR) 和淀粉样蛋白-β聚集在心血管疾病 (CVD) 患者中的复杂关系。一组 250 名表现出 CVD 症状的患者和 50 名对照者参加了这项研究。在应用严格的纳入和排除标准后，疾病组进一步分为三类：CVD+（阿尔茨海默病）AD、CVD+（糖尿病）DM 和 CVD+DM+AD。从所有招募的参与者中采集血液样本，用于生化分析脂质谱、血糖状态、肝功能酶、炎症和氧化应激生物标志物。四扩增反应性突变系统聚合酶链反应 (ARMS-PCR) 用于 APOE 基因分析。生化评估显示，在 CVD+DM+AD 组中，血清葡萄糖、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) 的水平显著升高。相反，与对照组和其他 CVD 组相比，CVD+DM+AD 组的血清胰岛素、HDL 和己糖激酶水平降低。四 ARMS-PCR 结果表明，与其他组相比，CVD+DM+AD 组的风险等位基因百分比更高。我们的研究阐明了导致 CVD 患者 IR 和 AD 的多种心血管危险因素。确定了与年龄相关的危险因素、APOE 风险等位基因的流行以及他汀类药物使用对 AD 发生率的影响。这些发现强调了需要采取有针对性的预防措施，特别是在患有 CVD 的 APOEε4 和 ε3/ε4 携带者中。进一步的研究应该深入研究基于知识的方案，以了解潜在的机制。关注治疗靶点，以预防或延缓 CVD 中 DM 和 AD 的进展，特别是在 APOEε4 携带者中，是至关重要的。
