Department of Biochemistry, Sir H.N. Medical Research Society, Mumbai, Maharashtra, India.
Department of Cardiology, Sir H.N. Reliance Foundation Hospital & Research Center, Mumbai, Maharashtra, India.
Indian J Med Res. 2020 Dec;152(6):607-613. doi: 10.4103/ijmr.IJMR_2112_18.
BACKGROUND & OBJECTIVES: Oxidative stress is known to have a causal role in hypertension. Klotho has emerged as a novel anti-aging molecule to inhibit oxidative stress at cellular level. This study aimed at evaluating the gene expression of klotho and antioxidative enzymes, manganese superoxide dismutase (Mn-SOD) and catalase, in peripheral blood mononuclear cells of essential hypertensive patients as compared to normotensive healthy controls.
Ninety-nine newly diagnosed hypertensives and 103 age- and BMI-matched controls were recruited. The participants were non-diabetic and not on any medication. Soluble α-klotho levels were detected using enzyme-linked immunosorbent assay. Gene expression was evaluated by quantitative real-time polymerase chain reaction.
Soluble α-klotho levels were significantly lower (27%, P=0.001) in patients as compared to controls. The trend remained same when compared against 44 out of 103 controls considered for gene expression analysis. Relative gene expression of klotho and catalase were 3-fold and 1.25-fold lower in patients as compared to controls, respectively. ΔCt value-based gene expression were also significantly lower for both genes (P=0.001). A decreasing but non-significant trend was observed for Mn-SOD gene expression. ΔCt value-based gene expression of catalase positively correlated with that of Mn-SOD in patient (rs=0.448) and control (rs=0.547) groups (P<0.001). In patients, the gene expression of Klotho positively correlated with that of catalase (rs=0.498, P=0.001), but not Mn-SOD (rs=0.155, P=0.126).
INTERPRETATION & CONCLUSIONS: In the present study on newly diagnosed hypertensives, klotho and catalase gene expression were found to be significantly lower as compared to controls, indicating the role of oxidative stress in this patient group. In addition, a significant correlation between Klotho and catalase gene expression suggests a role for klotho in essential hypertension with respect to antioxidant defence.
氧化应激被认为在高血压中起因果作用。Klotho 作为一种新的抗衰老分子,已被证明可在细胞水平抑制氧化应激。本研究旨在评估原发性高血压患者与血压正常的健康对照者外周血单个核细胞 klotho 基因和抗氧化酶(锰超氧化物歧化酶[Mn-SOD]和过氧化氢酶)的基因表达。
招募了 99 例新诊断的高血压患者和 103 例年龄和 BMI 匹配的对照组。参与者无糖尿病,且未服用任何药物。采用酶联免疫吸附试验检测可溶性α-Klotho 水平。采用实时定量聚合酶链反应评估基因表达。
与对照组相比,患者的可溶性α-Klotho 水平显著降低(27%,P=0.001)。当与 103 例对照组中的 44 例进行基因表达分析比较时,这种趋势仍然存在。与对照组相比,患者 klotho 和过氧化氢酶的相对基因表达分别降低了 3 倍和 1.25 倍。两种基因的ΔCt 值为基础的基因表达也显著降低(P=0.001)。Mn-SOD 基因表达呈下降趋势,但无统计学意义。在患者和对照组中,过氧化氢酶的ΔCt 值为基础的基因表达与 Mn-SOD 基因表达呈正相关(rs=0.448,rs=0.547,P<0.001)。在患者中,Klotho 基因表达与过氧化氢酶基因表达呈正相关(rs=0.498,P=0.001),但与 Mn-SOD 基因表达无关(rs=0.155,P=0.126)。
在本项对新诊断的高血压患者的研究中,klotho 和过氧化氢酶基因表达明显低于对照组,表明氧化应激在该患者群体中起作用。此外,Klotho 和过氧化氢酶基因表达之间存在显著相关性,提示 Klotho 在原发性高血压的抗氧化防御中发挥作用。