Post Graduation Program in Health Sciences, Santo Amaro University, Sao Paulo, Brazil.
Medicine Department, Cardiology Division, Federal University of Sao Paulo, Sao Paulo, Brazil.
Geriatr Gerontol Int. 2023 Sep;23(9):700-707. doi: 10.1111/ggi.14649. Epub 2023 Jul 31.
To evaluate the lipid-lowering and antiplatelet combined strategies on the expression of the receptors CCR2, CCR5, and CX3CR1 and the percentage of CCR2, CCR5, and CX3CR1 cells in monocyte subtypes after acute myocardial infarction.
Prospective, randomized, open-label study, with blinded analyses of endpoints (PROBE, ClinicalTrials.gov Identifier: NCT02428374, registration date: April 28, 2015). Participants were treated with rosuvastatin 20 mg or simvastatin 40 mg plus ezetimibe 10 mg, as well as ticagrelor 90 mg or clopidogrel 75 mg. The chemokine receptors CCR2, CCR5, and CX3CR1 were analyzed by real-time polymerase chain reaction as well as the percentages of CCR2, CCR5, and CX3CR1 cells in the monocyte subtypes (classical, intermediate, and non-classical), which were quantified by flow cytometry, at baseline, and after 1 and 6 months of treatment.
After comparisons between the three visits, regardless of the treatment arm, there was an increase in CCR2 expression after treatment, as well as an increase in intermediate monocytes CCR2+ and a reduction in non-classical monocytes CCR2+ at the end of treatment. There was also a lower expression of CCR5 after treatment and an increase in classical and non-classical monocytes CCR5+. Concerning CX3CR1, there were no differences in the expression after treatment; however, there were reductions in the percentage of intermediate and non-classical monocytes CX3CR1+ at the end of treatment.
The results suggest the persistence of the inflammatory phenotype, known as trained immunity, even with the highly-effective lipid-lowering and antiplatelet therapies. Geriatr Gerontol Int 2023; 23: 700-707.
评估降脂和抗血小板联合策略对急性心肌梗死后单核细胞亚型中受体 CCR2、CCR5 和 CX3CR1 的表达以及 CCR2、CCR5 和 CX3CR1 细胞百分比的影响。
这是一项前瞻性、随机、开放标签研究,终点分析采用盲法(PROBE,ClinicalTrials.gov 标识符:NCT02428374,注册日期:2015 年 4 月 28 日)。参与者接受瑞舒伐他汀 20mg 或辛伐他汀 40mg 加依折麦布 10mg 以及替格瑞洛 90mg 或氯吡格雷 75mg 治疗。通过实时聚合酶链反应分析趋化因子受体 CCR2、CCR5 和 CX3CR1,以及通过流式细胞术定量分析单核细胞亚型(经典型、中间型和非经典型)中 CCR2、CCR5 和 CX3CR1 细胞的百分比,在基线以及治疗 1 个月和 6 个月时进行测量。
无论治疗组如何,与三次就诊相比,治疗后 CCR2 表达增加,治疗结束时中间型单核细胞 CCR2+增加,非经典型单核细胞 CCR2+减少;CCR5 表达降低,经典型和非经典型单核细胞 CCR5+增加。治疗后 CX3CR1 表达无差异,但治疗结束时中间型和非经典型单核细胞 CX3CR1+百分比降低。
这些结果表明,即使采用高效的降脂和抗血小板治疗,炎症表型(即训练免疫)仍持续存在。