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首次证实醛固酮和血管钙化的正相关关系
发表日期: 2018-04-17 作者: 刘品明等 文章来源:《Hypertension》
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中山大学孙逸仙纪念医院的研究人员发表了题为“Downregulated Serum 14, 15-Epoxyeicosatrienoic Acid Is Associated With Abdominal Aortic Calcification in Patients With Primary Aldosteronism”的文章,首次在人群中证实了醛固酮和血管钙化的正相关关系,而且发现在肾功能受损提供的微环境下,醛固酮将发挥显著促进血管钙化的作用。

这一研究成果公布在Hypertension杂志上,文章的通讯作者为中山大学孙逸仙纪念医院黄辉教授和严励教授,第一作者为刘品明、张少玲、高静伟。

慢性肾脏疾病(Chronic Kidney Diseases, CKD)发病率在全球呈逐年上升趋势,我国成年人CKD患病率为10.8%(大约1.2亿)。尽管血液净化技术日新月异,但死亡率仍逐年攀升,现已明确导致CKD患者死亡最主要的原因是心血管并发症。该课题组的系列研究发现血管钙化在其中可能发挥更为重要作用。但目前针对血管钙化的治疗效果不理想,无论是药物、血管介入或外科手术都不能有效逆转,血管钙化发病机制是高血压和肾脏病领域的重要研究方向。

肾素-血管紧张素-醛固酮系统(Renin-Angiotensin-Aldosterone System, RAAS)CKD和心血管疾病的进程中都扮演极为重要的角色,表现为在心肾疾病中,RAAS均呈现过度激活,而增高的血管紧张素II和醛固酮是其中最为重要的效应分子,RAAS与血管钙化的关系一直也是人们研究的热点。

近年来研究发现,醛固酮能促进血管局部氧化应激、炎症,导致血管重构,但是醛固酮与血管钙化的关系一直有极大争议,尤其是缺乏人群研究的直接证据。另外,由于血浆醛固酮水平和血管钙化发生率在CKD中都显著上升,因此要在CKD明确两者是因果关系或并行关系有困难。

在这篇文章中,研究人员分析高血压人群数据,发现醛固酮与冠状动脉钙化并无关系。但是在肾功能受损的高血压人群中,随着血浆醛固酮水平的增高,血管钙化呈上升趋势。与年龄、血压和肾功能匹配的高血压患者相比,在肾功能受损原发性醛固酮增多症患者中,血浆骨形态发生蛋白等成骨因子明显升高,而腹主动脉钙化的发生率几乎增加一倍(39.1% vs 20.3%, P=0.023)。这说明在肾功能受损的环境下,醛固酮具有促血管钙化的作用。

此外还发现在腹主动脉钙化人群伴有14,15-二羟二十碳三烯酸(14,15-DHET)水平增高,而14,15-DHET是花生四烯酸细胞色素P450表氧化酶代谢产物14,15-EETs的降解物,该课题组长期从事这一通路的转化研究,也旁证调控14,15-EETs可能成为肾脏和心血管疾病的重要干预靶标。

这一研究首次在人群中证实了醛固酮和血管钙化的正相关关系,而且发现在肾功能受损提供的微环境下,醛固酮将发挥显著促进血管钙化的作用,同时找到了一个潜在的干预靶点14,15-EET,提供了全新角度去探讨醛固酮与血管钙化进展的关系,研究成果有望为血管钙化的治疗策略提供新思路。(来源:生物通)

 

Downregulated Serum 14, 15-Epoxyeicosatrienoic Acid Is Associated With Abdominal Aortic Calcification in Patients With Primary Aldosteronism

 

Abstract  Patients with primary aldosteronism (PA) have increased risk of target-organ damage, among which vascular calcification is an important indicator of cardiovascular mortality. 14, 15-Epoxyeicosatrienoic acid (14, 15-EET) has been shown to have beneficial effects in vascular remodeling. However, whether 14, 15-EET associates with vascular calcification in PA is unknown. Thus, we aimed to investigate the association between 14, 15-EET and abdominal aortic calcification (AAC) in patients with PA. Sixty-nine patients with PA and 69 controls with essential hypertension, matched for age, sex, and blood pressure, were studied. 14, 15-Dihydroxyeicosatrienoic acid (14, 15-DHET), the inactive metabolite from 14, 15-EET, was estimated to reflect serum 14, 15-EET levels. AAC was assessed by computed tomographic scanning. Compared with matched controls, the AAC prevalence was almost 1-fold higher in patients with PA (27 [39.1%] versus 14 [20.3%]; P=0.023), accompanied by significantly higher serum 14, 15-DHET levels (7.18±4.98 versus 3.50±2.07 ng/mL; P<0.001). Plasma aldosterone concentration was positively associated with 14, 15-DHET (β=0.444; P<0.001). Multivariable logistic analysis revealed that lower 14, 15-DHET was an independent risk factor for AAC in PA (odds ratio, 1.371; 95% confidence interval, 1.145–1.640; P<0.001), especially in young patients with mild hypertension and normal body mass index. In conclusion, PA patients exibited more severe AAC, accompanied by higher serum 14, 15-DHET levels. On the contrary, decreased 14, 15-EET was significantly associated with AAC prevalence in PA patients, especially in those at low cardiovascular risk.

 

原文链接:http://hyper.ahajournals.org/content/early/2018/02/09/HYPERTENSIONAHA.117.10644


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