Eguchi Masamichi, Ikeda Satoshi, Kusumoto Saburo, Sato Daisuke, Koide Yuji, Kawano Hiroaki, Maemura Koji
Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Life Sci. 2014 Nov 24;118(2):306-12. doi: 10.1016/j.lfs.2014.05.008. Epub 2014 May 20.
Functional and structural changes in pulmonary vasculature characterize pulmonary arterial hypertension (PAH) and the prognosis of advanced PAH remains poor despite progress in pharmacotherapy. Adipose-derived regenerative cells (ADRCs) promote cell regeneration at pathological sites and comprise a novel therapy for ailments of various organs. We investigated the effects of ADRC therapy in rat models of monocrotaline (MCT)-induced pulmonary hypertension (PH) and the underlying mechanisms.
Rats were assigned to Control and MCT groups without and with (M/A) intravenous transfusion of seven million ADRCs on day 7. We echocardiographically evaluated pulmonary hypertension as pulmonary artery flow acceleration time (PAAT) and deceleration (PADc). Right ventricular (RV) systolic pressure was measured by catheterization on day 28 and then pathological changes in pulmonary vessels were assessed. We analyzed PAH-associated gene expression on day 14 using real-time RT-PCR.
Echocardiography and RV catheterization showed that ADRC therapy inhibited PH development (assessed as PAAT, PADc, and RV systolic pressure) at day 28 (MCT vs. M/A, P<0.05). Pulmonary vascular remodeling was also inhibited (vessel wall thickness: MCT vs. M/A, P<0.01). Messenger RNA levels of endothelin (ET) A and B receptors, ET-1 and transforming growth factor (TGF)-β increased in the lungs by MCT were suppressed by ADRCs (MCT vs. M/A, P<0.05).
The development of PH was inhibited by ADRCs through suppressing changes in the expression of genes associated with ET and TGF-β systems. We believe that ADRC therapy could serve as a novel strategy for treating PH.
肺血管的功能和结构改变是肺动脉高压（PAH）的特征，尽管药物治疗取得了进展，但晚期PAH的预后仍然很差。脂肪来源的再生细胞（ADRCs）可促进病理部位的细胞再生，并构成一种针对各种器官疾病的新型治疗方法。我们研究了ADRC治疗在野百合碱（MCT）诱导的肺动脉高压（PH）大鼠模型中的作用及其潜在机制。
将大鼠分为对照组和MCT组，MCT组在第7天接受或不接受（M/A）七百万个ADRCs的静脉输注。我们通过超声心动图评估肺动脉高压，以肺动脉血流加速时间（PAAT）和减速时间（PADc）来衡量。在第28天通过导管插入术测量右心室（RV）收缩压，然后评估肺血管的病理变化。我们在第14天使用实时RT-PCR分析PAH相关基因的表达。
超声心动图和RV导管插入术显示，ADRC治疗在第28天抑制了PH的发展（以PAAT、PADc和RV收缩压评估）（MCT组与M/A组相比，P<0.05）。肺血管重塑也受到抑制（血管壁厚度：MCT组与M/A组相比，P<0.01）。MCT使肺中内皮素（ET）A和B受体、ET-1和转化生长因子（TGF）-β的信使RNA水平升高，而ADRCs抑制了这些升高（MCT组与M/A组相比，P<0.05）。
ADRCs通过抑制与ET和TGF-β系统相关基因表达的变化来抑制PH的发展。我们认为ADRC治疗可作为治疗PH的一种新策略。
