Orefice Valeria, Ceccarelli Fulvia, Barbati Cristiana, Buoncuore Giorgia, Pirone Carmelo, Alessandri Cristiano, Conti Fabrizio
Lupus Clinic, Rheumatology, Department of Clinical, Internal, Anesthesiologic and Cardiovascular, Sciences, Sapienza University of Rome, Rome, Italy.
Rheumatology (Oxford). 2025 Apr 1;64(4):1886-1893. doi: 10.1093/rheumatology/keae453.
We studied the role of caffeine intake on endothelial function in SLE by assessing its effect on circulating endothelial progenitor cells (EPCs) both ex vivo in SLE patients and in vitro in healthy donors (HD) treated with SLE sera.
We enrolled SLE patients without traditional cardiovascular risks factors. Caffeine intake was evaluated with a 7-day food frequency questionnaire. EPCs percentage was assessed by flow cytometry analysis and, subsequently, EPCs pooled from six HD were co-cultured with caffeine with and without SLE sera. After 7 days, we evaluated cells' morphology and ability to form colonies, the percentage of apoptotic cells by flow cytometry analysis and the levels of autophagy and apoptotic markers by western blot. Finally, we performed a western blot analysis to assess the A2AR/SIRT3/AMPK pathway.
We enrolled 31 SLE patients, and observed a positive correlation between caffeine intake and circulating EPCs percentage. HD EPCs treated with SLE sera and caffeine showed an improvement in morphology and in number of EPCs colony-forming units in comparison with those incubated without caffeine. Caffeine was able to restore autophagy and apoptotic markers in HD EPCs as before SLE sera treatment. Finally, caffeine treatment was able to significantly reduce A2AR levels, leading to an increase in protein levels of SIRT3 and subsequently AMPK phosphorylation.
Caffeine intake positively correlated with the percentage of circulating EPCs in SLE patients; moreover, caffeine in vitro treatment was able to improve EPC survival and vitality through the inhibition of apoptosis and the promotion of autophagy via A2AR/SIRT3/AMPK pathway.
通过评估咖啡因摄入对系统性红斑狼疮（SLE）患者循环内皮祖细胞（EPCs）的影响，研究其在SLE内皮功能中的作用，包括在SLE患者体内外以及用SLE血清处理的健康供体（HD）体外实验。
纳入无传统心血管危险因素的SLE患者。通过7天食物频率问卷评估咖啡因摄入量。采用流式细胞术分析评估EPCs百分比，随后将来自6名HD的EPCs与咖啡因在有或无SLE血清的情况下共培养。7天后，评估细胞形态、形成集落的能力、通过流式细胞术分析凋亡细胞百分比以及通过蛋白质印迹法检测自噬和凋亡标志物水平。最后，进行蛋白质印迹分析以评估A2AR/SIRT3/AMPK通路。
纳入31例SLE患者，观察到咖啡因摄入量与循环EPCs百分比呈正相关。与未用咖啡因孵育的HD EPCs相比，用SLE血清和咖啡因处理的HD EPCs在形态和EPCs集落形成单位数量上有改善。咖啡因能够像在SLE血清处理前一样恢复HD EPCs中的自噬和凋亡标志物。最后，咖啡因处理能够显著降低A2AR水平，导致SIRT3蛋白水平升高，随后AMPK磷酸化增加。
SLE患者咖啡因摄入量与循环EPCs百分比呈正相关；此外，体外咖啡因处理能够通过抑制凋亡和经由A2AR/SIRT3/AMPK通路促进自噬来改善EPCs的存活和活力。
