Department of Respiratory Therapy, Faculty of Medical Rehabilitation Sciences, King Abdulaziz University, Jeddah 22230, Saudi Arabia.
Medicina (Kaunas). 2023 Jan 13;59(1):165. doi: 10.3390/medicina59010165.
Pulmonary hypertension due to chronic obstructive pulmonary disease (COPD) is classified as Group 3 pulmonary hypertension, with no current proven targeted therapies. It has been shown that cigarette smoke, the main risk factor for COPD, can increase thromboxane A production in healthy human pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, and that blocking the effect of increased thromboxane A using daltroban, a thromboxane A receptor antagonist, can inhibit cigarette smoke-induced pulmonary artery cell proliferation. However, it is largely unknown whether thromboxane A is increased in smokers with COPD. Therefore, the aim of this study was to assess the level of thromboxane A production in patients with COPD who smoke. Pulmonary artery smooth muscle cells from three smokers with COPD and three healthy donors were cultured in cell culture medium. The culture medium was collected and the thromboxane B (a stable metabolite of thromboxane A) released in the culture medium was quantified using an ELISA kit. The data were normalised with the total protein concentration and then expressed in pg/mg protein. Demographic data were collected and baseline pulmonary function tests of patients with COPD were conducted. The mean age of patients with COPD was 69 ± 7 years. All patients were smokers and had a mean smoking history of 39.66 ± 9.50 packs per year. The mean forced expiratory volume in one second, that is, FEV1%, and the ratio of forced vital capacity (FVC) to FEV1% of COPD patients were 63.33 ± 19.60% and 52.66 ± 14.64%, respectively. The results revealed that thromboxane A production was significantly increased in pulmonary artery smooth muscle cells from smokers with COPD (434.56 ± 82.88 pg/mg protein) compared with the thromboxane levels in pulmonary artery smooth muscle cells from healthy donors (160 ± 59.3 pg/mg protein). This is the first report of increased thromboxane A production in pulmonary artery smooth muscle cells from smokers with COPD. This observation strongly suggests that thromboxane A can be used as a novel therapeutic target for the treatment of patients with COPD-associated pulmonary hypertension.
由慢性阻塞性肺疾病（COPD）引起的肺动脉高压被归类为第 3 组肺动脉高压，目前尚无经过验证的靶向治疗方法。研究表明，香烟烟雾是 COPD 的主要危险因素，可增加健康人肺动脉平滑肌细胞和肺血管内皮细胞中血栓素 A 的产生，而使用血栓素 A 受体拮抗剂 daltroban 阻断增加的血栓素 A 的作用，可以抑制香烟烟雾引起的肺动脉细胞增殖。然而，目前还不完全清楚吸烟者的血栓素 A 是否增加。因此，本研究旨在评估吸烟的 COPD 患者中血栓素 A 的产生水平。 将 3 名吸烟的 COPD 患者和 3 名健康供体的肺动脉平滑肌细胞在细胞培养基中培养。收集培养基，并使用 ELISA 试剂盒定量测定培养基中释放的血栓素 B（血栓素 A 的稳定代谢物）。将数据用总蛋白浓度归一化，然后以 pg/mg 蛋白表示。收集人口统计学数据并进行 COPD 患者的基线肺功能测试。 COPD 患者的平均年龄为 69 ± 7 岁。所有患者均为吸烟者，平均吸烟史为 39.66 ± 9.50 包/年。COPD 患者的 1 秒用力呼气量，即 FEV1%，以及用力肺活量（FVC）与 FEV1%的比值分别为 63.33 ± 19.60%和 52.66 ± 14.64%。结果表明，与健康供体的肺动脉平滑肌细胞中的血栓素 A 水平（160 ± 59.3 pg/mg 蛋白）相比，吸烟的 COPD 患者的肺动脉平滑肌细胞中的血栓素 A 生成明显增加（434.56 ± 82.88 pg/mg 蛋白）。 这是首次报道吸烟的 COPD 患者的肺动脉平滑肌细胞中血栓素 A 生成增加。这一观察结果强烈表明，血栓素 A 可用作治疗 COPD 相关肺动脉高压患者的新型治疗靶点。
