Experimental and Clinical Research Center (ECRC), a joint institution of the Charité Medical Faculty and Max Delbrück Center (MDC) for Molecular Medicine, Berlin 13125, Germany.
LIPIDOMIX GmbH, Robert-Rössle-Str. 10, Berlin 13125, Germany.
Prostaglandins Leukot Essent Fatty Acids. 2022 Jun;181:102453. doi: 10.1016/j.plefa.2022.102453. Epub 2022 May 21.
Cardiovascular disease is the leading cause of mortality in patients with renal failure. Red blood cells (RBCs) are potential reservoirs for epoxy fatty acids (oxylipins) that regulate cardiovascular function. Hemoglobin exhibits pseudo-lipoxygenase activity in vitro. We previously assessed the impact of single hemodialysis (HD) treatment on RBC epoxy fatty acids status in circulating arterial blood and found that eicosanoids in oxygenated RBCs could be particularly vulnerable in chronic kidney disease and hemodialysis. The purpose of the present study was to evaluate the differences of RBC epoxy fatty acids profiles in arterial and venous blood in vivo (AV differences) from patients treated by HD treatment. We collected arterial and venous blood samples in upper limbs from 12 end-stage renal disease (ESRD) patients (age 72±12 years) before and after HD treatment. We measured oxylipins derived from cytochrome P450 (CYP) monooxygenase and lipoxygenase (LOX)/CYP ω/(ω-1)-hydroxylase pathways in RBCs by LC-MS/MS tandem mass spectrometry. Our data demonstrate arteriovenous differences in LOX pathway metabolites in RBCs after dialysis, including numerous hydroxyeicosatetraenoic acids (HETEs), hydroxydocosahexaenoic acids (HDHAs) and hydroxyeicosapentaenoic acids (HEPEs). We detected more pronounced changes in free metabolites in RBCs after HD, as compared with the total RBC compartment. Hemodialysis treatment did not affect the majority of CYP and CYP ω/(ω-1)-hydroxylase products in RBCs. Our data indicate that erythro-metabolites of the LOX pathway are influenced by renal-replacement therapies, which could have deleterious effects in the circulation.
心血管疾病是肾衰竭患者死亡的主要原因。红细胞 (RBC) 是调节心血管功能的环氧脂肪酸 (氧化脂质) 的潜在储库。血红蛋白在体外具有拟脂氧合酶活性。我们之前评估了单次血液透析 (HD) 治疗对循环动脉血中 RBC 环氧脂肪酸状态的影响，发现含氧 RBC 中的类二十烷酸在慢性肾脏病和血液透析中可能特别脆弱。本研究的目的是评估 HD 治疗患者体内动脉血和静脉血中 RBC 环氧脂肪酸谱的差异 (AV 差异)。我们从 12 例终末期肾病 (ESRD) 患者 (年龄 72±12 岁) 的上肢采集动脉和静脉血样本，在 HD 治疗前后进行。我们通过 LC-MS/MS 串联质谱法测量 RBC 中细胞色素 P450 (CYP) 单加氧酶和脂氧合酶 (LOX)/CYP ω/(ω-1)-羟化酶途径衍生的氧化脂质。我们的数据表明，透析后 RBC 中的 LOX 途径代谢物存在动静脉差异，包括许多羟二十碳四烯酸 (HETE)、羟二十二碳六烯酸 (HDHA) 和羟二十碳五烯酸 (HEPE)。与 RBC 总隔室相比，我们在 HD 后检测到 RBC 中游离代谢物的变化更为明显。HD 治疗不影响 RBC 中的大多数 CYP 和 CYP ω/(ω-1)-羟化酶产物。我们的数据表明，LOX 途径的红细胞代谢物受肾脏替代治疗的影响，这可能对循环系统产生有害影响。
