Lefebvre Frederic, Préfontaine Annick, Calderone Angelino, Caron Alexandre, Jasmin Jean-François, Villeneuve Louis, Dupuis Jocelyn
Research Center of the Montreal Heart Institute, 5000 Belanger Street, Montréal, Québec, Canada H1T 1C8.
Clin Sci (Lond). 2006 Sep;111(3):217-24. doi: 10.1042/CS20060027.
Lung structural remodelling, characterized by myofibroblast proliferation and collagen deposition, contributes to impaired functional capacity in CHF (congestive heart failure). As the lung is the primary site for the formation of Ang II (angiotensin II), local modifications of this system could contribute to lung remodelling. Rats with CHF, induced following myocardial infarction (MI) via coronary artery ligation, were compared with sham-operated controls. The MI group developed lung remodelling as confirmed by morphometric measurements and immunohistochemistry. Pulmonary Ang II concentrations increased more than 6-fold (P<0.01), and AT1 (Ang II type 1) receptor expression was elevated by 3-fold (P<0.01) with evidence of distribution in myofibroblasts. AT2 (Ang II type 2) receptor expression was unchanged. In isolated lung myofibroblasts, AT1 and AT2 receptors were expressed, and Ang II stimulated proliferation as measured by [3H]thymidine incorporation. In normal rats, chronic intravenous infusion of Ang II (0.5 mg.kg(-1) of body weight.day(-1)) for 28 days significantly increased mean arterial pressure (P<0.05), without pulmonary hypertension, lung remodelling or a change in AT1 receptor expression. We conclude that there is a modification of the pulmonary renin-angiotensin system in CHF, with increased Ang II levels and AT1 receptor expression on myofibroblasts. Although this may contribute to lung remodelling, the lack of effect of increased plasma Ang II levels alone suggests the importance of local pulmonary Ang II levels combined with the effect of other factors activated in CHF.
以肌成纤维细胞增殖和胶原沉积为特征的肺结构重塑，会导致充血性心力衰竭（CHF）患者的功能能力受损。由于肺是血管紧张素II（Ang II）形成的主要部位，该系统的局部改变可能会导致肺重塑。将通过冠状动脉结扎诱导心肌梗死（MI）后出现CHF的大鼠与假手术对照组进行比较。形态计量学测量和免疫组织化学证实，MI组出现了肺重塑。肺组织中Ang II浓度增加了6倍以上（P<0.01），1型血管紧张素II（AT1）受体表达升高了3倍（P<0.01），且有证据表明其在肌成纤维细胞中分布。2型血管紧张素II（AT2）受体表达未发生变化。在分离的肺肌成纤维细胞中，AT1和AT2受体均有表达，Ang II通过[3H]胸腺嘧啶核苷掺入法测量可刺激细胞增殖。在正常大鼠中，连续28天慢性静脉输注Ang II（0.5 mg·kg-1体重·天-1）可显著升高平均动脉压（P<0.05），但未出现肺动脉高压、肺重塑或AT1受体表达改变。我们得出结论，CHF患者存在肺肾素-血管紧张素系统的改变，肌成纤维细胞上的Ang II水平升高且AT1受体表达增加。尽管这可能有助于肺重塑，但仅血浆Ang II水平升高缺乏效应表明局部肺Ang II水平与CHF中激活的其他因素的作用相结合的重要性。
