Tory Rita, Sachs-Barrable Kristina, Goshko Caylee-Britt, Hill John S, Wasan Kishor M
Faculty of Medicine, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Transplantation. 2009 Jul 15;88(1):62-8. doi: 10.1097/TP.0b013e3181aa7d04.
Hyperlipidemia is a frequent and persistent complication in solid organ transplant recipients, leading to the high occurrence of cardiovascular disease in this patient population. Lipid abnormalities including increased total cholesterol, triglycerides (TG), and low-density lipoprotein-cholesterol have been reported frequently in transplantation patients and a variety of immunosuppressive therapies seem to be one of the main factors that influence posttransplant lipidemic profiles. For many years, tacrolimus (TAC) has been used as an immunosuppressive drug in transplantation. The aim of our investigation was to determine the effect of TAC administration on the plasma lipid profile and some key regulatory proteins of plasma lipid metabolism including cholesterol ester transfer protein, hepatic lipase and lipoprotein lipase (LPL) within renal transplant patients.
Twenty-five renal transplant patients were recruited and received TAC therapy, of which nine of these patients were treated with statin therapy for dyslipidemia. The effects of TAC on plasma total cholesterol, TG, HDL-C, low-density lipoprotein-cholesterol, cholesterol ester transfer protein, hepatic lipase and LPL concentration and activity were determined from patients plasma samples collected before the transplant surgery (baseline), and weekly for four consecutive weeks after surgery and TAC administration.
We observed that TAC significantly increases plasma TG concentrations and reduces LPL plasma concentration and activity in renal transplant patients, independent of any lipid lowering drug treatment patients received.
Taken together, these findings suggest that the reduction in LPL activity, partly due to the decrease of plasma LPL concentration after TAC administration may be an explanation for hypertriglyceridemia observed in patients administered TAC.
高脂血症是实体器官移植受者常见且持续存在的并发症,导致该患者群体中心血管疾病的高发生率。移植患者中经常报告脂质异常,包括总胆固醇、甘油三酯(TG)和低密度脂蛋白胆固醇升高,多种免疫抑制疗法似乎是影响移植后血脂谱的主要因素之一。多年来,他克莫司(TAC)一直被用作移植中的免疫抑制药物。我们研究的目的是确定在肾移植患者中给予TAC对血脂谱以及血脂代谢的一些关键调节蛋白(包括胆固醇酯转运蛋白、肝脂酶和脂蛋白脂酶(LPL))的影响。
招募了25名接受TAC治疗的肾移植患者,其中9名患者因血脂异常接受他汀类药物治疗。从移植手术前(基线)以及手术后和给予TAC后连续四周每周采集的患者血浆样本中,测定TAC对血浆总胆固醇、TG、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、胆固醇酯转运蛋白、肝脂酶和LPL浓度及活性的影响。
我们观察到,在肾移植患者中,TAC显著增加血浆TG浓度,并降低血浆LPL浓度和活性,这与患者接受的任何降脂药物治疗无关。
综上所述,这些发现表明,LPL活性降低,部分原因是给予TAC后血浆LPL浓度降低,这可能是在接受TAC治疗的患者中观察到高甘油三酯血症的一个原因。