Lomelí Oscar, Pérez-Torres Israel, Márquez Ricardo, Críales Sergio, Mejía Ana M, Chiney Claudia, Hernández-Lemus Enrique, Soto Maria E
Department of Echocardiography, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico.
Department of Pathology, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico.
Front Physiol. 2018 Aug 21;9:965. doi: 10.3389/fphys.2018.00965. eCollection 2018.
Marfan syndrome (MS) is of the most common connective tissue disorders. Although most patients have mutations in the fibrillin-1 gene (FBN1) and more than 1,700 mutations have been described, there are no mutations in less than 10% of patients. Aortic dilation is the most important complication; it involves chronic inflammatory processes and endothelial dysfunction. Prospective study from March 2015 to January 2017, in a cohort of 32 patients of MS confirmed by Ghent criteria and 35 controls of both genders, with a median age of 26 years (18-56). Patients had no comorbidities such as diabetes, hypertension, and/or neoplasms. They were not being treated with statin, NSAIDs, calcium antagonists, oral nitrates, and/or beta-blockers during 7 days prior to the study and patients with smoking history in the last 4 years. Controls were matched by age and gender. We analyzed endothelial dysfunction by flow-mediated vasodilation in the brachial artery, determining the maximum peak flow in the reactive hyperemia phase with a Philips Envisor device with Doppler capability. Its correlation with serum levels of biological markers that could participate in endothelial dysfunction pathways such as ratio, , citrulline, TNFα, IL-1, IL-6, IL-10, IL-8, osteopontin, ICAM, VCAM, and was determined. Endothelial dysfunction was found in 21 MS patients (65%). The aortic annulus (AAo) was of 27 mm (22-40) and 24 mm (22-30) ( = 0.04) in MS patients with and without dysfunction. The level of ratio, was of 108.95 ± 12.05 nM/ml in controls vs. 170.04 ± 18.76 nM/ml in MS ( = 0.002), was of 33.78 ± 3.41 vs. 43.95 ± 2.59 nM/ml ( = 0.03), citrulline 62.65 ± 3.46 vs. 72.81 ± 4.35 μMol/ml ( = 0.06). VCAM median was 39 pg/ml (0-86) vs. 32 pg/ml (11-66) ( = 0.03), respectively. The correlation of VCAM with triglycerides (TG) was of 0.62 ( = 0.005). There were no differences in TNFα, IL-1, IL-6, IL-8, IL-10, and osteopontin. MS endothelial dysfunction is related to aortic diameters, and increased levels of VCAM, L-citrulline and ratio, . VCAM-1 has a significant correlation with TG and could play a significant role in endothelial dysfunction.
马凡综合征（MS）是最常见的结缔组织疾病之一。虽然大多数患者存在原纤蛋白-1基因（FBN1）突变，且已描述了1700多种突变，但仍有不到10%的患者未发生突变。主动脉扩张是最重要的并发症；它涉及慢性炎症过程和内皮功能障碍。2015年3月至2017年1月进行的一项前瞻性研究，纳入了32例经根特标准确诊的MS患者和35名对照者，男女均有，中位年龄为26岁（18 - 56岁）。患者无糖尿病、高血压和/或肿瘤等合并症。在研究前7天内未接受他汀类药物、非甾体抗炎药、钙拮抗剂、口服硝酸盐和/或β受体阻滞剂治疗，且过去4年内无吸烟史。对照者按年龄和性别匹配。我们通过肱动脉的血流介导的血管舒张来分析内皮功能障碍，使用具有多普勒功能的飞利浦Envisor设备测定反应性充血期的最大峰值血流。确定其与可能参与内皮功能障碍途径的生物标志物血清水平的相关性，如比值、 、瓜氨酸、TNFα、IL - 1、IL - 6、IL - 10、IL - 8、骨桥蛋白、ICAM、VCAM和 。在21例MS患者（65%）中发现了内皮功能障碍。有内皮功能障碍和无内皮功能障碍的MS患者的主动脉环（AAo）分别为27 mm（22 - 40）和24 mm（22 - 30）（P = 0.04）。对照组的比值水平为108.95±12.05 nM/ml，而MS患者为170.04±18.76 nM/ml（P = 0.002）， 为33.78±3.41 vs. 43.95±2.59 nM/ml（P = 0.03），瓜氨酸为62.65±3.46 vs. 72.81±4.35 μMol/ml（P = 0.06）。VCAM中位数分别为39 pg/ml（0 - 86）和32 pg/ml（11 - 66）（P = 0.03）。VCAM与甘油三酯（TG）的相关性为0.62（P = 0.005）。TNFα、IL - 1、IL - 6、IL - 8、IL - 10和骨桥蛋白无差异。MS内皮功能障碍与主动脉直径以及VCAM、L - 瓜氨酸和比值 、 的水平升高有关。VCAM - 与TG有显著相关性，可能在内皮功能障碍中起重要作用。
