Nosalski Ryszard, McGinnigle Eilidh, Siedlinski Mateusz, Guzik Tomasz J
BHF Centre for Excellence Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland UK.
Department of Internal and Agricultural Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Curr Cardiovasc Risk Rep. 2017;11(4):12. doi: 10.1007/s12170-017-0537-6. Epub 2017 Mar 6.
Hypertension is a common disorder with substantial impact on public health due to highly elevated cardiovascular risk. The mechanisms still remain unclear and treatments are not sufficient to reduce risk in majority of patients. Inflammatory mechanisms may provide an important mechanism linking hypertension and cardiovascular risk. We aim to review newly identified immune and inflammatory mechanisms of hypertension with focus on their potential therapeutic impact.
In addition to the established role of the vasculature, kidneys and central nervous system in pathogenesis of hypertension, low-grade inflammation contributes to this disorder as indicated by experimental models and GWAS studies pointing to SH2B3 immune gene as top key driver of hypertension. Immune responses in hypertension are greatly driven by neoantigens generated by oxidative stress and modulated by chemokines such as RANTES, IP-10 and microRNAs including miR-21 and miR-155 with other molecules under investigation. Cells of both innate and adoptive immune system infiltrate vasculature and kidneys, affecting their function by releasing pro-inflammatory mediators and reactive oxygen species.
Immune and inflammatory mechanisms of hypertension provide a link between high blood pressure and increased cardiovascular risk, and reduction of blood pressure without attention to these underlying mechanisms is not sufficient to reduce risk.
高血压是一种常见疾病,因其导致心血管风险大幅升高,对公众健康产生重大影响。其发病机制仍不明确,且多数患者的治疗不足以降低风险。炎症机制可能是连接高血压与心血管风险的重要机制。我们旨在综述新发现的高血压免疫和炎症机制,重点关注其潜在治疗作用。
除了血管、肾脏和中枢神经系统在高血压发病机制中已确定的作用外,实验模型和全基因组关联研究表明,低度炎症也参与其中,这些研究指出SH2B3免疫基因是高血压的首要关键驱动因素。高血压中的免疫反应很大程度上由氧化应激产生的新抗原驱动,并受趋化因子(如RANTES、IP-10)和微小RNA(包括miR-21和miR-155)以及其他正在研究的分子调节。固有免疫系统和适应性免疫系统的细胞浸润血管和肾脏,通过释放促炎介质和活性氧来影响其功能。
高血压的免疫和炎症机制在高血压与心血管风险增加之间建立了联系,不关注这些潜在机制而单纯降低血压不足以降低风险。