Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
Am J Physiol Heart Circ Physiol. 2019 Nov 1;317(5):H1093-H1101. doi: 10.1152/ajpheart.00416.2019. Epub 2019 Sep 6.
Pulmonary arterial hypertension (PAH) is a fatal disease with a median survival of only 5-7 yr. PAH is characterized by remodeling of the pulmonary vasculature causing reduced pulmonary arterial compliance (PAC) and increased pulmonary vascular resistance (PVR), ultimately resulting in right ventricular failure and death. Better therapies for PAH will require a paradigm shift in our understanding of the early pathophysiology. PAC decreases before there is an increase in the PVR. Unfortunately, present treatment has little effect on PAC. The loss of compliance correlates with extracellular matrix remodeling and fibrosis in the pulmonary vessels, which have been linked to chronic perivascular inflammation and immune dysregulation. However, what initiates the perivascular inflammation and immune dysregulation in PAH is unclear. Alteration of the gut microbiota composition and function underlies the level of immunopathogenic involvement in several diseases, including atherosclerosis, obesity, diabetes mellitus, and depression, among others. In this review, we discuss evidence that raises the possibility of an etiologic role for changes in the gut and circulating microbiome in the initiation of perivascular inflammation in the early pathogenesis of PAH.
肺动脉高压（PAH）是一种致命疾病，中位生存时间仅为 5-7 年。PAH 的特征是肺血管重构，导致肺动脉顺应性（PAC）降低和肺血管阻力（PVR）增加，最终导致右心室衰竭和死亡。更好的 PAH 治疗方法需要改变我们对早期病理生理学的理解。在 PVR 增加之前，PAC 就会下降。不幸的是，目前的治疗方法对 PAC 几乎没有影响。顺应性的丧失与肺血管中细胞外基质重构和纤维化相关，这与慢性血管周围炎症和免疫失调有关。然而，PAH 中引发血管周围炎症和免疫失调的原因尚不清楚。肠道微生物组组成和功能的改变是多种疾病（包括动脉粥样硬化、肥胖、糖尿病和抑郁症等）中免疫致病作用的基础。在这篇综述中，我们讨论了一些证据，这些证据提出了这样一种可能性，即肠道和循环微生物组的变化可能在 PAH 的早期发病机制中引发血管周围炎症的发生。
