Szabó Dorottya, Benkő László, Lőrinczy Dénes
Department of Vascular Surgery, Medical School, University of Pécs, Pécs Ifjúság Str. 13, H-7624 Pecs, Hungary.
Department of Biophysics, Medical School, University of Pécs, Pécs Szigeti Str. 12, H-7624 Pecs, Hungary.
Pharmaceuticals (Basel). 2025 Jun 13;18(6):886. doi: 10.3390/ph18060886.
: Intermittent claudication, an early symptom of peripheral artery disease, can be treated by cilostazol to alleviate symptoms and improve walking distance. Our previous investigation focused on cilostazol-induced alterations in the thermodynamic properties of plasma, utilizing differential scanning calorimetry (DSC) as a potential monitoring tool. The current proof-of-concept study aimed to enhance the interpretation of DSC data through deconvolution techniques, specifically examining protein transitions within the plasma proteome during cilostazol therapy. : Notable differences in thermal unfolding profiles were found between cilostazol-treated patients and healthy controls. The fibrinogen-associated transition exhibited a downward shift in denaturation temperature and decreased enthalpy by the third month. The albumin-related transition shifted to higher temperatures, accompanied by lower enthalpy. Transitions associated with globulins showed changes in thermal stability, while the transferrin-related peak demonstrated increased structural rigidity in treated patients compared to controls. : These observations suggest that cilostazol induces systemic changes in the thermodynamic behavior of plasma proteins. DSC, when combined with deconvolution methods, presents a promising approach for detecting subtle, therapy-related alterations in plasma protein stability. : Ten patients (median age: 58.6 years) received 100 milligrams of cilostazol twice daily. Blood samples were collected at the baseline and after 2 weeks, 1 month, 2 months, and 3 months of therapy. Walking distances were also assessed. The DSC curves were retrieved from the thermal analysis investigated by deconvolution mathematical methods. : Although the exact functional consequences remain unclear, the observed biophysical changes may reflect broader molecular adaptations involving protein-protein interactions, post-translational modifications, or acute phase response elements.
间歇性跛行是外周动脉疾病的早期症状，西洛他唑可用于治疗以缓解症状并增加行走距离。我们之前的研究聚焦于西洛他唑引起的血浆热力学性质变化，利用差示扫描量热法（DSC）作为一种潜在的监测工具。当前的概念验证研究旨在通过去卷积技术增强对DSC数据的解读，具体研究西洛他唑治疗期间血浆蛋白质组中的蛋白质转变。
在接受西洛他唑治疗的患者和健康对照之间发现了热解折叠曲线的显著差异。与纤维蛋白原相关的转变在变性温度上出现向下偏移，到第三个月时焓降低。与白蛋白相关的转变向更高温度偏移，同时焓降低。与球蛋白相关的转变显示出热稳定性的变化，而与转铁蛋白相关的峰在治疗患者中相比于对照表现出结构刚性增加。
这些观察结果表明西洛他唑诱导血浆蛋白热力学行为的全身性变化。DSC与去卷积方法相结合，为检测血浆蛋白稳定性中与治疗相关的细微变化提供了一种有前景的方法。
10名患者（中位年龄：58.6岁）每天两次接受100毫克西洛他唑治疗。在基线以及治疗2周、1个月、2个月和3个月后采集血样。还评估了行走距离。通过去卷积数学方法从热分析中获取DSC曲线。
尽管确切的功能后果仍不清楚，但观察到的生物物理变化可能反映了涉及蛋白质 - 蛋白质相互作用、翻译后修饰或急性期反应元件的更广泛的分子适应性变化。
