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他汀类药物治疗与狭窄主动脉瓣中抗动脉粥样硬化因子C型利钠肽系统的基因表达

Statin treatment and gene expression of anti-atherogenic factor C-type natriuretic peptide system in stenotic aortic valves.

作者信息

Peltonen Tuomas, Ohtonen Pasi, Näpänkangas Juha, Ohukainen Pauli, Ruskoaho Heikki, Taskinen Panu

机构信息

Institution of Biomedicine, Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Finland.

出版信息

J Heart Valve Dis. 2011 Sep;20(5):545-51.

Abstract

AIMS

Aortic valve calcification is an actively regulated process with endothelial dysfunction displaying hallmarks of atherosclerosis. C-type natriuretic peptide (CNP) system has been reported to have a role in the pathogenesis of vascular atherosclerosis and to be distinctly downregulated in aortic valve stenosis (AS). Here we studied gene expressions of CNP and is target receptor natriuretic peptide receptor type B (NPR-B) in human aortic valves. Furthermore, we compared gene expression of CNP system in patients with HMG-coenzyme-A reductase (statin) treatment to non-statin-treated patients in AS group.

METHODS AND RESULTS

With the study population of 108 patients, we characterized expression of CNP and NPR-B in human aortic valves and compared normal control valves (n = 12) with valves obtained from patients with aortic regurgitation (AR, n = 16), AR with fibrosis (AR+fibr., n = 19) and AS (n = 61). By reverse transcription-polymerase chain reaction (RT-PCR), CNP mRNA levels were 89% lower (p = 0.022) in stenotic valves, when compared to AR group. Moreover, the mRNA levels of NPR-B, the target receptor of CNP, were 62% lower (p < 0.001) in stenotic valves when compared to control group and 54% lower (p = 0.002) in stenotic valves, when compared to AR group. There was no statistical significant difference in CNP and NPR-B levels in AS group when the statin-treated patients were compared to untreated patients.

CONCLUSIONS

These results show for the first time that the gene expression of anti-atherogenic CNP system did not differ between statin-treated and non-statin-treated patients in AS. The research data supports the results of clinical trials with the same drug class.

摘要

目的

主动脉瓣钙化是一个受主动调节的过程,伴有显示动脉粥样硬化特征的内皮功能障碍。据报道,C型利钠肽(CNP)系统在血管动脉粥样硬化的发病机制中起作用,并且在主动脉瓣狭窄(AS)中明显下调。在此,我们研究了人主动脉瓣中CNP及其靶受体B型利钠肽受体(NPR-B)的基因表达。此外,我们比较了AS组中接受HMG辅酶A还原酶(他汀类药物)治疗的患者与未接受他汀类药物治疗的患者中CNP系统的基因表达。

方法和结果

在108例患者的研究人群中,我们对人主动脉瓣中CNP和NPR-B的表达进行了表征,并将正常对照瓣膜(n = 12)与来自主动脉瓣反流(AR,n = 16)、伴有纤维化的AR(AR + 纤维化,n = 19)和AS(n = 61)患者的瓣膜进行了比较。通过逆转录聚合酶链反应(RT-PCR),与AR组相比,狭窄瓣膜中的CNP mRNA水平降低了89%(p = 0.022)。此外,与对照组相比,狭窄瓣膜中CNP的靶受体NPR-B的mRNA水平降低了62%(p < 0.001),与AR组相比,狭窄瓣膜中的NPR-B的mRNA水平降低了54%(p = 0.002)。在AS组中,将接受他汀类药物治疗的患者与未治疗的患者进行比较时,CNP和NPR-B水平没有统计学上的显著差异。

结论

这些结果首次表明,在AS中,接受他汀类药物治疗和未接受他汀类药物治疗的患者之间,抗动脉粥样硬化CNP系统的基因表达没有差异。该研究数据支持了使用同一类药物的临床试验结果。

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