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健康个体短期阿托伐他汀治疗导致血浆基质金属蛋白酶水平未改变,且基质金属蛋白酶-7与血脂及血细胞计数衍生的炎症标志物之间的相关性被破坏。

Short-Term Atorvastatin Therapy in Healthy Individuals Results in Unaltered Plasma MMP Levels and Disrupted MMP-7 Correlation with Blood Lipids and Blood Count-Derived Inflammatory Markers.

作者信息

Mănescu Ion Bogdan, Mănescu Măriuca, Bărcuțean Laura Iulia, Demian Liliana, Dobreanu Minodora

机构信息

Department of Laboratory Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 38 Gheorghe Marinescu, 540142 Targu Mures, Romania.

Department of Pediatrics, Emergency County Clinical Hospital of Targu Mures, 50 Gheorghe Marinescu, 540136 Targu Mures, Romania.

出版信息

J Clin Med. 2024 Aug 13;13(16):4743. doi: 10.3390/jcm13164743.

Abstract

: Matrix metalloproteinases (MMPs) play an important role in the pathophysiology of atherosclerosis. Reportedly, statins can decrease MMP activity in patients with atherosclerotic cardiovascular disease, but this effect has not been studied in healthy individuals. : MMPs 2, 7, and 9 and several other parameters were measured before and after a four-week course of moderate-dose atorvastatin (20 mg/day) in 21 healthy individuals. : Atorvastatin treatment resulted in lower total cholesterol, LDL-cholesterol, non-HDL-cholesterol, and triglycerides ( < 0.001 for all), but higher levels of plasma enzymes AST, ALT, CK, and LDH ( < 0.05 for all). No effect of atorvastatin on plasma MMP median concentrations was recorded. Before treatment, moderate positive significant correlations were found between MMP-7 and age, blood lipids, and blood count-derived inflammatory markers. Pre-treatment MMP-7 was best predicted by the total cholesterol-to-HDL cholesterol ratio in a remnant cholesterol-weighted least squares regression model. After atorvastatin treatment, MMP-7 no longer correlated with these markers. : While the effect of statins on plasma MMPs in atherosclerosis is controversial, short-term moderate-dose atorvastatin treatment does not seem to affect levels of MMPs 2, 7, and 9 in healthy individuals. However, an intriguing correlation between MMP-7 and atherosclerosis-related blood lipids and neutrophil-associated inflammatory biomarkers seems to be disrupted by atorvastatin independently of hsCRP, possibly via pleiotropic effects.

摘要

基质金属蛋白酶(MMPs)在动脉粥样硬化的病理生理学中起重要作用。据报道,他汀类药物可降低动脉粥样硬化性心血管疾病患者的MMP活性,但尚未在健康个体中研究这种作用。在21名健康个体中,在给予为期四周的中等剂量阿托伐他汀(20毫克/天)疗程前后,测量了MMPs 2、7和9以及其他几个参数。阿托伐他汀治疗导致总胆固醇、低密度脂蛋白胆固醇、非高密度脂蛋白胆固醇和甘油三酯水平降低(所有均P<0.001),但血浆酶AST、ALT、CK和LDH水平升高(所有均P<0.05)。未记录到阿托伐他汀对血浆MMP中位数浓度有影响。治疗前,发现MMP-7与年龄、血脂和血细胞计数衍生的炎症标志物之间存在中度正相关。在残粒胆固醇加权最小二乘回归模型中,总胆固醇与高密度脂蛋白胆固醇之比对治疗前的MMP-7预测效果最佳。阿托伐他汀治疗后,MMP-7不再与这些标志物相关。虽然他汀类药物对动脉粥样硬化患者血浆MMPs的影响存在争议,但短期中等剂量阿托伐他汀治疗似乎不会影响健康个体中MMPs 2、7和9的水平。然而,阿托伐他汀似乎独立于hsCRP破坏了MMP-7与动脉粥样硬化相关血脂和中性粒细胞相关炎症生物标志物之间的有趣相关性,可能是通过多效性作用。

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