Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe 610-0395, Kyoto, Japan.
Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmachi, Suita 564-8565, Osaka, Japan.
Int J Mol Sci. 2023 Jan 21;24(3):2167. doi: 10.3390/ijms24032167.
Cardiomyopathy is the leading cause of death in patients with muscular dystrophy (MD). Tranilast, a widely used anti-allergic drug, has displayed inhibitory activity against the transient receptor potential cation channel subfamily V member 2 and improved cardiac function in MD patients. To identify urinary biomarkers that assess improved cardiac function after tranilast administration, we performed a urinary metabolomic study focused on oxidative fatty acids. Accompanying the clinical trial of tranilast, urine specimens were collected over 24 weeks from MD patients with advanced heart failure. Urinary levels of tetranor-PGDM (tetranor-prostaglandin D metabolite), a metabolite of prostaglandin D, significantly decreased 12 weeks after tranilast administration and were correlated with BNP. These results suggest that prostaglandin-mediated inflammation, which increases with the pathological progression of heart failure in MD patients, was attenuated. Urinary prostaglandin E (PGE) levels significantly increased 4 weeks after tranilast administration. There were positive correlations between the urinary levels of PGE and 8-hydroxy-2'-deoxyguanosine, an oxidative stress marker. High PGE levels may have a protective effect against cardiomyopathy in MD patients with high oxidative stress. Although further validation studies are necessary, urinary tetranor-PGDM and PGE levels may help the current understanding of the extent of advanced heart failure in patients with MD after tranilast administration.
心肌病是肌肉萎缩症（MD）患者死亡的主要原因。曲尼司特是一种广泛使用的抗过敏药物，对瞬时受体电位阳离子通道亚家族 V 成员 2 具有抑制活性，并改善了 MD 患者的心脏功能。为了确定评估曲尼司特给药后心脏功能改善的尿生物标志物，我们进行了一项专注于氧化脂肪酸的尿代谢组学研究。在曲尼司特临床试验的同时，从患有晚期心力衰竭的 MD 患者中收集了 24 周的尿液标本。前列腺素 D 代谢物四氢前列腺素 D（tetranor-prostaglandin D metabolite）的尿水平在曲尼司特给药 12 周后显著降低，与 BNP 相关。这些结果表明，前列腺素介导的炎症随着 MD 患者心力衰竭的病理进展而增加，其被减弱。曲尼司特给药 4 周后，尿前列腺素 E（PGE）水平显著增加。尿 PGE 水平与氧化应激标志物 8-羟基-2'-脱氧鸟苷之间存在正相关。高 PGE 水平可能对高氧化应激的 MD 患者的心肌病具有保护作用。尽管需要进一步的验证研究，但尿四氢前列腺素 D 和 PGE 水平可能有助于当前理解曲尼司特给药后 MD 患者晚期心力衰竭的程度。
