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Key inflammatory pathways underlying vascular remodeling in pulmonary hypertension

机译:肺动脉高压下血管重塑的关键炎症途径

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Independent of the underlying cause, pulmonary hypertension (PH) remains adevastating condition that is characterized by limited survival. Cumulating evidence indicates that in addition to adysbalance of mediators regulating vascular tone and growth factors promoting vascular remodeling, failure to resolve inflammation and altered immune processes play apivotal role in the development and progression of PH. Here, we highlight the role of key inflammatory pathways in the pathobiology of vascular remodeling and PH, and discuss potential therapeutic interventions that may halt disease progression or even reverse pulmonary vascular remodeling. Perivascular inflammation is present in all forms of PH, and inflammatory pathways involve numerous mediators and cell types including macrophages, neutrophils, Tcells, dendritic cells, and mast cells. Dysfunctional bone morphogenic protein receptor2 (BMPR2) signaling and dysregulated immunity enable the accumulation of macrophages and other inflammatory cells in obliterative vascular lesions. Regulatory Tcells (Tregs) were shown to be of particular relevance in the control of inflammatory responses. Key cytokines/chemokines include interleukin-6, functioning via classic or trans-signaling, macrophage migratory inhibitory factor (MIF), but also other mediators such as neutrophil-derived myeloperoxidase. The expanding knowledge on this topic has resulted in multiple opportunities for sophisticated therapeutic interventions.
机译:独立于潜在的原因,肺动脉高压(pH)仍然是adevapated病症,其特征在于存活有限。累积证据表明,除了调节血管间调和促进血管重塑的血管间调和生长因素的诱导患者的易紊乱外,未能解决炎症和改变的免疫过程在pH的发展和进展中发挥亚波的作用。在这里,我们突出了关键炎症途径在血管重塑和pH的病理学中的作用,并讨论可能停止疾病进展甚至逆向肺血管重塑的潜在治疗干预措施。血管外炎症以所有形式的pH存在,炎症途径涉及许多介质和细胞类型,包括巨噬细胞,中性粒细胞,Tcells,树突细胞和肥大细胞。功能障碍骨形态发生蛋白受体2(BMPR2)信号传导和失调的免疫使巨噬细胞和其他炎症细胞的积累在灭错的血管病变中。监管Tcells(Tregs)被证明在炎症反应中具有特别相关性。键细胞因子/趋化因子包括白细胞介素-6,通过经典或反式信号传导,巨噬细胞迁移抑制因子(MIF)起作用,而且还具有其他介质,例如中性粒细胞衍生的髓过氧化物酶。对本课题的扩展知识导致了复杂的治疗干预措施的多种机会。

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