McCarthy Cameron G, Webb R Clinton
Department of Physiology, Georgia Regents University, Augusta, Georgia, USA
Department of Physiology, Georgia Regents University, Augusta, Georgia, USA.
FASEB J. 2016 Jan;30(1):34-40. doi: 10.1096/fj.15-279588. Epub 2015 Aug 27.
American football has unequivocally been linked to elevations in blood pressure and hypertension, especially in linemen. However, the mechanisms of this increase cannot be attributed solely to increased body weight and associated cardiometabolic risk factors (e.g.,dyslipidemia or hyperglycemia). Therefore, understanding the etiology of football-associated hypertension is essential for improving the quality of life in this mostly young population, as well as for lowering the potential for chronic disease in the future. We propose that inflammatogenic damage-associated molecular patterns (DAMPs) released into the circulation from football-induced musculoskeletal trauma activate pattern-recognition receptors of the innate immune system-specifically, high mobility group box 1 protein (HMGB1) and mitochondrial (mt)DNA which activate Toll-like receptor (TLR)4 and -9, respectively. Previously, we observed that circulating levels of these 2 DAMPs are increased in hypertension, and activation of TLR4 and -9 causes endothelial dysfunction and hypertension. Therefore, our novel hypothesis is that musculoskeletal injury from repeated hits in football players, particularly in linemen, leads to elevated circulating HMGB1 and mtDNA to activate TLRs on endothelial cells leading to impaired endothelium-dependent vasodilation, increased vascular tone, and hypertension.
美式橄榄球已明确与血压升高和高血压有关，尤其是在前锋球员中。然而，血压升高的机制不能仅仅归因于体重增加及相关的心脏代谢风险因素（如血脂异常或高血糖）。因此，了解与橄榄球相关的高血压的病因，对于改善这个以年轻人为主的群体的生活质量，以及降低未来患慢性病的可能性至关重要。我们提出，橄榄球运动引起的肌肉骨骼创伤释放到循环系统中的促炎损伤相关分子模式（DAMPs）激活了先天免疫系统的模式识别受体，具体而言，即高迁移率族蛋白盒1（HMGB1）和线粒体（mt）DNA，它们分别激活Toll样受体（TLR）4和-9。此前，我们观察到这两种DAMPs的循环水平在高血压患者中升高，并且TLR4和-9的激活会导致内皮功能障碍和高血压。因此，我们的新假设是，橄榄球运动员，尤其是前锋球员，因反复撞击造成的肌肉骨骼损伤会导致循环中的HMGB1和mtDNA升高，从而激活内皮细胞上的TLR，导致内皮依赖性血管舒张受损、血管张力增加和高血压。
