Dutzmann Jochen, Daniel Jan-Marcus, Bauersachs Johann, Hilfiker-Kleiner Denise, Sedding Daniel G
Vascular Remodeling and Regeneration Group, Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany.
Vascular Remodeling and Regeneration Group, Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany
Cardiovasc Res. 2015 Jun 1;106(3):365-74. doi: 10.1093/cvr/cvv103. Epub 2015 Mar 17.
Acute and chronic inflammation responses characterize the vascular remodelling processes in atherosclerosis, restenosis, pulmonary arterial hypertension, and angiogenesis. The functional and phenotypic changes in diverse vascular cell types are mediated by complex signalling cascades that initiate and control genetic reprogramming. The signalling molecule's signal transducer and activator of transcription 3 (STAT3) plays a key role in the initiation and continuation of these pathophysiological changes. This review highlights the pivotal involvement of STAT3 in pathological vascular remodelling processes and discusses potential translational therapies, which target STAT3 signalling, to prevent and treat cardiovascular diseases. Moreover, current clinical trials using highly effective and selective inhibitors of STAT3 signalling for distinct diseases, such as myelofibrosis and rheumatoid arthritis, are discussed with regard to their vascular (side-) effects and their potential to pave the way for a direct use of these molecules for the prevention or treatment of vascular diseases.
急性和慢性炎症反应是动脉粥样硬化、再狭窄、肺动脉高压和血管生成中血管重塑过程的特征。多种血管细胞类型的功能和表型变化由启动和控制基因重编程的复杂信号级联介导。信号分子信号转导子和转录激活子3(STAT3)在这些病理生理变化的启动和持续过程中起关键作用。本综述强调了STAT3在病理性血管重塑过程中的关键作用,并讨论了针对STAT3信号传导的潜在转化疗法,以预防和治疗心血管疾病。此外,还讨论了目前针对骨髓纤维化和类风湿关节炎等不同疾病使用STAT3信号传导高效和选择性抑制剂的临床试验,涉及它们的血管(副)作用以及为直接使用这些分子预防或治疗血管疾病铺平道路的潜力。