Increased Thromboxane A<sub>2</sub> Levels in Pulmonary Artery Smooth Muscle Cells Isolated from Patients with Chronic Obstructive Pulmonary Disease
<i>Introduction:</i> 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<...
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| フォーマット: | 論文 |
| 言語: | English |
| 出版事項: |
MDPI AG
2023-01-01
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| シリーズ: | Medicina |
| 主題: | |
| オンライン･アクセス: | https://www.mdpi.com/1648-9144/59/1/165 |
| 要約: | <i>Introduction:</i> 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<sub>2</sub> production in healthy human pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, and that blocking the effect of increased thromboxane A<sub>2</sub> using daltroban, a thromboxane A<sub>2</sub> receptor antagonist, can inhibit cigarette smoke-induced pulmonary artery cell proliferation. However, it is largely unknown whether thromboxane A<sub>2</sub> is increased in smokers with COPD. Therefore, the aim of this study was to assess the level of thromboxane A<sub>2</sub> production in patients with COPD who smoke. <i>Methods:</i> 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<sub>2</sub> (a stable metabolite of thromboxane A<sub>2</sub>) 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. <i>Results:</i> 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<sub>2</sub> 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 <sub>A2</sub> levels in pulmonary artery smooth muscle cells from healthy donors (160 ± 59.3 pg/mg protein). <i>Conclusions:</i> This is the first report of increased thromboxane A<sub>2</sub> production in pulmonary artery smooth muscle cells from smokers with COPD. This observation strongly suggests that thromboxane A<sub>2</sub> can be used as a novel therapeutic target for the treatment of patients with COPD-associated pulmonary hypertension. |
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| ISSN: | 1010-660X 1648-9144 |