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klotho蛋白:对原发性高血压发病机制的新见解。

Klotho protein: a new insight into the pathogenesis of essential hypertension.

作者信息

Awasthi Richa, Manger Priyanka Thapa, Khare Rajesh Kumar, Alam Roshan

机构信息

Department of Biochemistry, Integral Institute of Medical Sciences and Research, Integral University, Lucknow, India.

Department of Medicine, Integral Institute of Medical Sciences and Research, Integral University, Lucknow, India.

出版信息

Clin Hypertens. 2024 Dec 1;30(1):36. doi: 10.1186/s40885-024-00294-5.

Abstract

BACKGROUND

Essential hypertension is a most prevalent global health concern. Despite extensive research, the exact mechanisms contributing to essential hypertension remain unclear. Several factors contribute to the pathogenesis of essential hypertension. Klotho, a membrane-bound and soluble protein, has been found to modulate hypertension through physiological processes like vascular function and sodium balance. This study aimed to determine the association of klotho protein with essential hypertension.

METHODS

The study included 164 hypertensive cases and 164 normotensive controls, after imposing certain inclusion and exclusion criteria with written consent from all subjects. Subject's details were obtained using structured proforma to account for potential confounding variables. To estimate klotho protein activity using sandwich enzyme-linked immunosorbent assay, 2 mL blood was collected in a plain vial. All data were tested at a 5% significance level.

RESULTS

The analysis revealed a significant decrease in klotho protein levels in cases compared to controls (1.52 ± 0.87 vs. 2.45 ± 0.90, P < 0.001), suggesting an inverse relationship of klotho protein with risk of essential hypertension. All indices in the structural equation model have suggested that the final model fitted the data reasonably (chi-square to df ratio, 1.153; goodness of fit index, 0.990; adjusted goodness of fit index, 0.945; normed fit index, 0.936; standardized root mean square residual, 0.953; root mean square error of approximation, 0.031). Also, klotho was negatively associated with blood pressure. The area under the receiver operating characteristic curve for klotho and blood pressure was 0.765 (95% confidence interval, 0.716-0.815; P < 0.001).

CONCLUSIONS

Klotho levels were significantly reduced in essential hypertension cases compared to controls, Also, klotho had a negative direct association with essential hypertension indicating a potential role for klotho as a prognostic and predictive marker for essential hypertension. This suggests that klotho may have a role in the pathogenesis of essential hypertension. Understanding klotho's role in essential hypertension may lead to the development of novel therapeutic strategies for this disease.

摘要

背景

原发性高血压是全球最普遍的健康问题。尽管进行了广泛研究,但导致原发性高血压的确切机制仍不清楚。有几个因素促成了原发性高血压的发病机制。Klotho是一种膜结合和可溶性蛋白,已发现它通过血管功能和钠平衡等生理过程调节高血压。本研究旨在确定Klotho蛋白与原发性高血压之间的关联。

方法

在所有受试者签署书面同意书并施加一定的纳入和排除标准后,该研究纳入了164例高血压病例和164例血压正常的对照。使用结构化表格获取受试者的详细信息,以考虑潜在的混杂变量。为了使用夹心酶联免疫吸附测定法估计Klotho蛋白活性,在普通试管中采集2 mL血液。所有数据均在5%的显著性水平上进行检验。

结果

分析显示,与对照组相比,病例组中Klotho蛋白水平显著降低(1.52±0.87对2.45±0.90,P<0.001),表明Klotho蛋白与原发性高血压风险呈负相关。结构方程模型中的所有指标均表明最终模型与数据拟合合理(卡方与自由度之比为1.153;拟合优度指数为0.990;调整后拟合优度指数为0.945;规范拟合指数为0.936;标准化均方根残差为0.953;近似均方根误差为0.031)。此外,Klotho与血压呈负相关。Klotho与血压的受试者工作特征曲线下面积为0.765(95%置信区间为0.716 - 0.815;P<0.001)。

结论

与对照组相比,原发性高血压病例中的Klotho水平显著降低。此外,Klotho与原发性高血压呈负向直接关联,表明Klotho作为原发性高血压的预后和预测标志物具有潜在作用。这表明Klotho可能在原发性高血压的发病机制中起作用。了解Klotho在原发性高血压中的作用可能会导致针对该疾病开发新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13ae/11608492/2c0037bb3ab1/40885_2024_294_Fig1_HTML.jpg

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