Department of Clinical and Biological Sciences of Turin University, 10043 Orbassano, Turin, Italy.
Metabolic Disease and Diabetes Unit, San Luigi Gonzaga Hospital, 10043 Orbassano, Turin, Italy.
Int J Mol Sci. 2020 Jul 15;21(14):4983. doi: 10.3390/ijms21144983.
Platelet hyperactivation is involved in the established prothrombotic condition of metabolic diseases such as Type 2 Diabetes Mellitus (T2DM) and familial hypercholesterolemia (HC), justifying the therapy with aspirin, a suppressor of thromboxane synthesis through the irreversible inhibition of cyclooxygenase-1 (COX-1), to prevent cardiovascular diseases. However, some patients on aspirin show a higher than expected platelet reactivity due, at least in part, to a pro-oxidant milieu. The aim of this study was to investigate platelet reactivity in T2DM ( = 103) or HC ( = 61) patients (aspirin, 100 mg/day) and its correlation with biomarkers of redox function including the superoxide anion scavenger superoxide dismutase (SOD) and the in vivo marker of oxidative stress urinary 8-iso-prostaglandin F. As results, in T2DM and HC subjects the prevalence of high on-aspirin platelet reactivity was comparable when both non-COX-1-dependent and COX-1-dependent assays were performed, and platelet reactivity is associated with a lower SOD activity that in a stepwise linear regression appears as the only predictor of platelet reactivity. To conclude, in T2DM and HC, similarly, the impairment of redox equilibrium associated with a decrease of SOD activity could contribute to a suboptimal response to aspirin.
血小板过度激活与 2 型糖尿病(T2DM)和家族性高胆固醇血症(HC)等代谢疾病的既定血栓形成状态有关,这使得通过不可逆抑制环氧化酶-1(COX-1)来抑制血栓素合成的阿司匹林成为预防心血管疾病的一种治疗方法。然而,一些服用阿司匹林的患者表现出高于预期的血小板反应性,至少部分原因是由于促氧化剂环境。本研究旨在调查 T2DM(=103)或 HC(=61)患者(阿司匹林,100mg/天)的血小板反应性及其与氧化还原功能生物标志物的相关性,包括超氧阴离子清除剂超氧化物歧化酶(SOD)和体内氧化应激标志物 8-异前列腺素 F。结果显示,在 T2DM 和 HC 患者中,当同时进行非 COX-1 依赖性和 COX-1 依赖性检测时,高阿司匹林反应性血小板的发生率相当,并且血小板反应性与 SOD 活性降低相关,在逐步线性回归中,SOD 活性是血小板反应性的唯一预测因子。总之,在 T2DM 和 HC 中,同样地,与 SOD 活性降低相关的氧化还原平衡失调可能导致阿司匹林反应不佳。