Pulmonary arterial hypertension (PAH) is a rare, complex, and deadly cardiopulmonary disease. It is characterized by changes in endothelial cell function and smooth muscle cell proliferation in the pulmonary arteries, causing persistent vasoconstriction, resulting in right heart hypertrophy and failure. There are multiple drug classes specific to PAH treatment, but variation between patients may impact treatment response. A small subset of patients is responsive to pulmonary vasodilators and can be treated with calcium channel blockers, which would be deleterious if prescribed to a typical PAH patient. Little is known about the underlying cause of this important difference in vasoresponsive PAH patients. Sex, race/ethnicity, and pharmacogenomics may also factor into efficacy and safety of PAH-specific drugs. Research has indicated that endothelin receptor antagonists may be more effective in women and there have been some minor differences found in certain races and ethnicities, but these findings are muddled by the impact of socioeconomic factors and a lack of representation of non-White patients in clinical trials. Genetic variants in genes such as CYP3A5, CYP2C9, PTGIS, PTGIR, GNG2, CHST3, and CHST13 may influence the efficacy and safety of certain PAH-specific drugs. PAH research faces many challenges, but there is potential for new methodologies to glean new insights into PAH development and treatment.

中文翻译：

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肺动脉高压的不同药物反应：精准医疗的潜力

肺动脉高压（PAH）是一种罕见、复杂且致​​命的心肺疾病。其特点是肺动脉内皮细胞功能改变和平滑肌细胞增殖，引起持续性血管收缩，导致右心肥厚和衰竭。有多种针对 PAH 治疗的药物类别，但患者之间的差异可能会影响治疗反应。一小部分患者对肺血管扩张剂有反应，可以用钙通道阻滞剂治疗，但如果给典型的 PAH 患者开处方，这将是有害的。对于血管反应性 PAH 患者中这种重要差异的根本原因知之甚少。性别、种族/民族和药物基因组学也可能影响 PAH 特异性药物的功效和安全性。研究表明，内皮素受体拮抗剂可能对女性更有效，并且在某些种族和民族中发现了一些细微的差异，但这些发现因社会经济因素的影响以及临床中缺乏非白人患者的代表性而变得混乱。试验。CYP3A5、CYP2C9、PTGIS、PTGIR、GNG2、CHST3和CHST13等基因的遗传变异可能会影响某些 PAH 特异性药物的疗效和安全性。PAH 研究面临许多挑战，但新方法有可能为 PAH 的发展和治疗提供新的见解。