Barbaro Natália Ruggeri, de Araújo Thiago Matos, Tanus-Santos José Eduardo, Anhê Gabriel Forato, Fontana Vanessa, Moreno Heitor
Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, 13084971 Campinas, SP, Brazil.
Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, 13084971 Campinas, SP, Brazil.
Biomed Res Int. 2015;2015:631594. doi: 10.1155/2015/631594. Epub 2015 Oct 4.
Inflammatory cytokines have been associated with the pathophysiology of hypertension and target organ damage (TOD). Resistant hypertensive patients (RHTN) are characterized by poor blood pressure control and higher prevalence of TOD. This study evaluated the relationship between plasma levels of TNF-α and arterial stiffness (pulse wave velocity-PWV) in 32 RHTN and 19 normotensive subjects. Moreover, we investigated the effect of TNF-α inhibition on human endothelial cells (HUVECs) incubated with serum from RHTN and normotensive subjects. HUVECs containing serum obtained from normotensive (n = 8) and hypertensive (n = 8) individuals were treated with TNF-α inhibitor (infliximab). Cell suspensions were used for measurement of DNA fragmentation and reactive oxygen species (ROS) content. RHTN patients showed higher levels of TNF-α compared to normotensive subjects, as well as higher PWV. Positive correlation was found between TNF-α levels and PWV measures in the whole group. HUVECs incubated with serum from RHTN showed increased cell apoptosis and higher ROS content compared to normotensive subjects. Infliximab attenuated the apoptosis of HUVECs incubated with serum from RHTN, but no effect in ROS production was observed. Our findings suggest that TNF-α might mediate, at least in part, vascular damage in resistant hypertension.
炎症细胞因子与高血压及靶器官损害(TOD)的病理生理学相关。顽固性高血压患者(RHTN)的特点是血压控制不佳且TOD患病率较高。本研究评估了32例RHTN患者和19例血压正常受试者血浆中TNF-α水平与动脉僵硬度(脉搏波速度-PWV)之间的关系。此外,我们研究了TNF-α抑制对用RHTN和血压正常受试者血清孵育的人内皮细胞(HUVECs)的影响。用TNF-α抑制剂(英夫利昔单抗)处理含有从血压正常(n = 8)和高血压(n = 8)个体获得的血清的HUVECs。细胞悬液用于测量DNA片段化和活性氧(ROS)含量。与血压正常受试者相比,RHTN患者的TNF-α水平更高,PWV也更高。在整个组中发现TNF-α水平与PWV测量值之间呈正相关。与血压正常受试者相比,用RHTN血清孵育的HUVECs显示细胞凋亡增加和ROS含量更高。英夫利昔单抗减弱了用RHTN血清孵育的HUVECs的凋亡,但未观察到对ROS产生的影响。我们的研究结果表明,TNF-α可能至少部分介导了顽固性高血压中的血管损伤。