Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome 'tor Vergata', Rome, Italy.
Unit of Respiratory Disease and Lung Function, Department of Medicine and Surgery, University of Parma, Parma, Italy.
Int J Chron Obstruct Pulmon Dis. 2024 Nov 21;19:2481-2495. doi: 10.2147/COPD.S498255. eCollection 2024.
Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory condition often complicated by cardiovascular disease (CVD) due to shared inflammatory pathways. This review explores the cardiovascular impacts of emerging anti-inflammatory therapies in COPD. Phosphodiesterase (PDE) inhibitors may offer anti-inflammatory effects with improved lung function but pose potential risks for arrhythmias when PDE3 is inhibited although PDE4 inhibitors reduce cardiovascular events by improving endothelial function and reducing thrombosis. Similarly, p38 mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) inhibitors target COPD-related inflammation and may benefit COPD patients with CVD. p38 MAPK inhibitors reduce cardiac fibrosis, enhance contractility and lower the risk of arrhythmia. PI3K inhibitors target the PI3K/Akt pathway, which drives atherosclerosis and cardiac fibrosis, and thus potentially mitigate both plaque instability and fibrosis. Biologic therapies, including monoclonal antibodies that inhibit IL-5, IL-13/IL-4, thymic stromal lymphopoietin, IL-33, and IL-17A, show promise in reducing exacerbations but require close cardiovascular monitoring due to their immunomodulatory effects. Single-target inhibitors of neutrophil elastase or matrix metalloproteinases show limited efficacy in COPD but may aid cardiovascular patients by stabilizing atherosclerotic plaques through promoting vascular smooth muscle cell proliferation. However, their tendency to degrade the extracellular matrix and attract immune cells may heighten plaque rupture risk, contraindicating use in CVD. Alpha-1 antitrypsin replacement therapy holds promise, potentially reducing COPD exacerbations and providing cardiovascular protection, especially in myocardial injury. Understanding the influence of these innovative therapies on CVD is vital, making it imperative to examine these molecules in COPD patients with CVD at an early stage.
慢性阻塞性肺疾病（COPD）是一种进行性炎症性疾病，由于炎症途径的共享，常伴有心血管疾病（CVD）。本综述探讨了新兴抗炎疗法对 COPD 的心血管影响。磷酸二酯酶（PDE）抑制剂可能通过改善肺功能发挥抗炎作用，但当 PDE3 被抑制时，可能会有引发心律失常的风险，尽管 PDE4 抑制剂通过改善内皮功能和减少血栓形成来减少心血管事件。同样，p38 丝裂原活化蛋白激酶（MAPK）和磷酸肌醇 3-激酶（PI3K）抑制剂靶向 COPD 相关炎症，可能对患有 CVD 的 COPD 患者有益。p38 MAPK 抑制剂可减少心脏纤维化，增强收缩力，降低心律失常风险。PI3K 抑制剂靶向驱动动脉粥样硬化和心脏纤维化的 PI3K/Akt 通路，从而有可能减轻斑块不稳定和纤维化。生物疗法，包括抑制白细胞介素 5、白细胞介素 13/白细胞介素 4、胸腺基质淋巴生成素、白细胞介素 33 和白细胞介素 17A 的单克隆抗体，在减少恶化方面显示出希望，但由于其免疫调节作用，需要密切进行心血管监测。中性粒细胞弹性蛋白酶或基质金属蛋白酶的单靶点抑制剂在 COPD 中的疗效有限，但通过促进血管平滑肌细胞增殖稳定动脉粥样硬化斑块，可能对心血管患者有益。然而，它们降解细胞外基质和吸引免疫细胞的倾向可能会增加斑块破裂的风险，不建议将其用于 CVD。α-1 抗胰蛋白酶替代疗法有希望，可能会减少 COPD 恶化并提供心血管保护，特别是在心肌损伤方面。了解这些创新疗法对 CVD 的影响至关重要，因此必须在患有 CVD 的 COPD 患者中尽早检查这些分子。
