COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series).
COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series).
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DOI：
10.1177/2045894018758528
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发表时间：
2018-01
影响因子：
2.6
通讯作者：
Owen CA
中科院分区：
文献类型：
--
作者：
Polverino F;Celli BR;Owen CA
慢性阻塞性肺疾病（COPD）的特点是慢性呼气气流阻塞，不完全可逆。慢性阻塞性肺病患者会出现不同程度的肺气肿、小气道和大气道疾病以及各种合并症。目前尚不清楚这些合并症是否与肺部病变具有共同的潜在致病过程。早期对COPD发病机制的研究主要集中在细胞外基质和肺上皮细胞损伤方面。最近，吸烟引起的内皮功能障碍/损伤与慢性阻塞性肺病（COPD）的肺部病变（尤其是肺气肿）和全身合并症（包括动脉粥样硬化、肺动脉高压和慢性肾损伤）有关。在此，我们回顾了内皮损伤与COPD相关的证据，以及内皮损伤和“血管性COPD表型”的潜在途径，包括：(1)香烟烟雾对内皮细胞的直接毒性作用；(2)产生针对内皮细胞的自身抗体；(3)血管炎症；(4)血管中氧化应激水平升高，诱导脂质过氧化增加和晚期糖基化终产物受体（RAGE）的激活增加；(5)内皮细胞抗氧化途径的激活降低；(6)内皮细胞释放具有血管收缩、促炎和重塑活性的介质（内皮素-1）增加，内皮细胞表达促进血管舒张和内皮细胞稳态的介质（一氧化氮合酶和前列环素）减少；(7)内皮细胞内质网应激和未折叠蛋白反应增加。我们还回顾了在其他疾病（血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂）中抑制RAGE信号的药物的研究，或针对特发性肺动脉高压开发的血管扩张剂的研究，这些研究已经在细胞培养系统、COPD动物模型和/或吸烟者和COPD患者中进行了测试。
Chronic obstructive pulmonary disease (COPD) is characterized by chronic expiratory airflow obstruction that is not fully reversible. COPD patients develop varying degrees of emphysema, small and large airway disease, and various co-morbidities. It has not been clear whether these co-morbidities share common underlying pathogenic processes with the pulmonary lesions. Early research into the pathogenesis of COPD focused on the contributions of injury to the extracellular matrix and pulmonary epithelial cells. More recently, cigarette smoke-induced endothelial dysfunction/injury have been linked to the pulmonary lesions in COPD (especially emphysema) and systemic co-morbidities including atherosclerosis, pulmonary hypertension, and chronic renal injury. Herein, we review the evidence linking endothelial injury to COPD, and the pathways underlying endothelial injury and the “vascular COPD phenotype” including: (1) direct toxic effects of cigarette smoke on endothelial cells; (2) generation of auto-antibodies directed against endothelial cells; (3) vascular inflammation; (4) increased oxidative stress levels in vessels inducing increases in lipid peroxidation and increased activation of the receptor for advanced glycation end-products (RAGE); (5) reduced activation of the anti-oxidant pathways in endothelial cells; (6) increased endothelial cell release of mediators with vasoconstrictor, pro-inflammatory, and remodeling activities (endothelin-1) and reduced endothelial cell expression of mediators that promote vasodilation and homeostasis of endothelial cells (nitric oxide synthase and prostacyclin); and (7) increased endoplasmic reticular stress and the unfolded protein response in endothelial cells. We also review the literature on studies of drugs that inhibit RAGE signaling in other diseases (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), or vasodilators developed for idiopathic pulmonary arterial hypertension that have been tested on cell culture systems, animal models of COPD, and/or smokers and COPD patients.
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发表时间：
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影响因子：
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