Department of Cardiology, Medical Clinic 2, University Clinic Erlangen, Erlangen, Germany.
Department of Nephrology, Medical Clinic 4, University Clinic Erlangen, Erlangen, Germany.
Eur J Clin Invest. 2016 Jun;46(6):564-71. doi: 10.1111/eci.12635.
Growing evidence shows that inflammation plays a pivotal role in the pathophysiology of essential hypertension (EH). Although it is acknowledged that target organ damage involves an inflammatory response, most work has focused on the role of macrophages. However, recently, platelets were identified as inducing inflammation partly by releasing cytokines. The goal of our study was to evaluate the role of platelets as inflammatory cells in the pathogenesis of EH.
Thirty-nine patients with EH and 30 healthy normotensive controls have been examined. Expression of platelet CD40 was measured by flow cytometry. Serum levels of monocyte chemoattractant protein 1 (MCP-1) and sCD40L were measured via a multiplexing assay. In in vitro experiments, activated platelets were cocultured with human umbilical vein endothelial cells (HUVEC) in the presence and absence of anti-CD154 antibodies. MCP-1 in the supernatants was measured by EIA.
Essential hypertension patients showed significantly enhanced MCP-1 levels with highest levels in EH patients with microalbuminuria. EH patients showed increased expression of platelet CD40. In the cell coculture model, activated platelets were able to significantly induce MCP-1 release from HUVEC in a CD40L-dependent manner. EH patients showed elevated sCD40L levels with a positive correlation with MCP-1 levels.
Platelets can contribute to enhanced MCP-1 levels in EH. MCP-1 is markedly elevated in serum of EH patients with highest levels in patients with microalbuminuria, one early sign of renal target organ damage. Further studies are required to test whether MCP-1 blocking or antiplatelet strategies may represent new therapeutic options in preventing hypertensive target organ damage.
越来越多的证据表明，炎症在原发性高血压（EH）的病理生理学中起着关键作用。尽管人们承认靶器官损伤涉及炎症反应，但大多数研究都集中在巨噬细胞的作用上。然而，最近发现血小板通过释放细胞因子部分引起炎症。我们的研究旨在评估血小板作为炎症细胞在 EH 发病机制中的作用。
检查了 39 名 EH 患者和 30 名健康的正常血压对照者。通过流式细胞术测量血小板 CD40 的表达。通过多重分析测定单核细胞趋化蛋白 1（MCP-1）和 sCD40L 的血清水平。在体外实验中，在存在和不存在抗 CD154 抗体的情况下，将活化的血小板与人脐静脉内皮细胞（HUVEC）共培养。通过 EIA 测量上清液中的 MCP-1。
EH 患者的 MCP-1 水平明显升高，微量白蛋白尿的 EH 患者水平最高。EH 患者表现出血小板 CD40 表达增加。在细胞共培养模型中，活化的血小板能够以 CD40L 依赖性方式显著诱导 HUVEC 释放 MCP-1。EH 患者的 sCD40L 水平升高，并与 MCP-1 水平呈正相关。
血小板可导致 EH 中 MCP-1 水平升高。EH 患者的 MCP-1 血清水平明显升高，微量白蛋白尿的患者水平最高，这是肾脏靶器官损伤的早期迹象之一。需要进一步研究以测试 MCP-1 阻断或抗血小板策略是否可能代表预防高血压靶器官损伤的新治疗选择。
