Particulate matter (PM) adverse effects on health include lung and heart damage. The renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) endocrine systems are involved in the pathophysiology of cardiovascular diseases and have been found to impact lung diseases. The aim of the present study was to evaluate whether PM exposure regulates elements of RAAS and KKS. Sprague–Dawley rats were acutely (3 days) and subchronically (8 weeks) exposed to coarse (CP), fine (FP) or ultrafine (UFP) particulates using a particulate concentrator, and a control group exposed to filtered air (FA). We evaluated the mRNA of the RAAS components At1, At2r and Ace, and of the KKS components B1r, B2r and Klk-1 by RT-PCR in the lungs and heart. The ACE and AT1R protein were evaluated by Western blot, as were HO-1 and γGCSc as indicators of the antioxidant response and IL-6 levels as an inflammation marker. We performed a binding assay to determinate AT1R density in the lung, also the subcellular AT1R distribution in the lungs was evaluated. Finally, we performed a histological analysis of intramyocardial coronary arteries and the expression of markers of heart gene reprogramming (Acta1 and Col3a1). The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner. CP exposure induced Ace mRNA expression and regulated its protein in the lungs. Acute and subchronic exposure to FP and UFP induced the expression of At1r in the lungs and heart. All PM fractions increased the AT1R protein in a size-dependent manner in the lungs and heart after subchronic exposure. The AT1R lung protein showed a time-dependent change in subcellular distribution. In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6. Moreover, exposure to all PM fractions increased coronary artery wall thickness. We demonstrate that exposure to PM induces the expression of RAAS and KKS elements, including AT1R, which was the main target in the lungs and the heart.

中文翻译：

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急性和亚慢性暴露于空气颗粒物会诱导肺和心脏中血管紧张素和缓激肽相关基因的表达：血管紧张素II型I受体是暴露于颗粒物的分子靶标。

颗粒物（PM）对健康的不利影响包括肺部和心脏损害。肾素-血管紧张素-醛固酮（RAAS）和激肽释放酶-激肽（KKS）内分泌系统参与心血管疾病的病理生理，并已发现会影响肺部疾病。本研究的目的是评估PM暴露是否调节RAAS和KKS的元素。使用颗粒浓缩器将Sprague-Dawley大鼠急性（3天）和亚慢性（8周）暴露于粗颗粒（CP），细颗粒（FP）或超细颗粒（UFP），对照组暴露于过滤空气（FA）。我们通过RT-PCR在肺和心脏中评估了RAAS成分At1，At2r和Ace以及KKS成分B1r，B2r和Klk-1的mRNA。ACE和AT1R蛋白通过Western blot进行评估，HO-1和γGCSc作为抗氧化剂反应的指标，IL-6水平作为炎症指标。我们进行了结合测定以确定肺中AT1R的密度，还评估了肺中亚细胞AT1R的分布。最后，我们进行了心肌内冠状动脉的组织学分析以及心脏基因重编程标记（Acta1和Col3a1）的表达。PM组分以时间依赖性方式诱导肺和心脏中RAAS和KKS元素的表达。CP暴露诱导肺中Ace mRNA表达并调节其蛋白质。FP和UFP的急性和亚慢性暴露诱导肺和心脏中At1r的表达。亚慢性暴露后，肺和心脏中所有PM组分均以大小依赖的方式增加AT1R蛋白。AT1R肺蛋白在亚细胞分布中显示出时间依赖性变化。此外，心脏中AT1R的存在伴随HO-1的减少，这与Acta1和Col3a1的诱导以及IL-6的增加同时发生。此外，暴露于所有PM组分会增加冠状动脉壁的厚度。我们证明暴露于PM会诱导RAAS和KKS元素（包括AT1R）的表达，AT1R是肺和心脏的主要靶标。