Sirolimus Therapy Is Associated with Elevation in Circulating PCSK9 Levels in Cardiac Transplant Patients.
Sirolimus Therapy Is Associated with Elevation in Circulating PCSK9 Levels in Cardiac Transplant Patients.
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DOI：
10.1007/s12265-016-9719-8
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发表时间：
2017-02
影响因子：
3.4
通讯作者：
Pereira NL
中科院分区：
文献类型：
--
作者：
Simha V;Qin S;Shah P;Smith BH;Kremers WK;Kushwaha S;Wang L;Pereira NL
用于移植的西罗莫司通常与高胆固醇血症有关。我们测量了51例心脏移植受者的血脂和PCSK 9水平，这些受者的免疫抑制治疗从钙调磷酸酶抑制剂转换为西罗莫司。转换导致LDL胆固醇升高23%，甘油三酯升高46%，PCSK 9水平从316 ± 105 ng/mL升高至343 ± 107 ng/mL（p=0.04），但PCSK 9水平的变化与脂质水平升高无关（p=0.2）。为了研究PCSK 9水平变化的可变性机制，将淋巴母细胞系与西罗莫司和依维莫司一起孵育，导致mTOR抑制剂敏感性细胞系中PCSK 9表达和蛋白质水平增加2-3倍，但在mTOR抑制剂抗性细胞系中没有。这是首次人体研究，证明西罗莫司治疗与PCSK 9水平升高相关，而PCSK 9水平升高与西罗莫司诱导的高胆固醇血症无关。
Sirolimus used in transplantation is often associated with hypercholesterolemia. We measured serum lipid and PCSK9 levels in 51 heart transplant recipients who had their immunosuppressive therapy switched from calcineurin inhibitors to sirolimus. The switch resulted in a 23% increase in LDL cholesterol, and 46% increase in triglycerides and PCSK9 levels increased from 316 ± 105 ng/mL to 343 ± 107 ng/mL (p=0.04), however the change in PCSK9 levels did not correlate with an increase in lipid levels (p=0.2). To investigate the mechanism for the variability in the change in PCSK9 levels, lymphoblastoid cell lines were incubated with both sirolimus and everolimus, resulting in a 2–3 fold increase in PCSK9 expression and protein levels in mTOR inhibitor sensitive but not in mTOR inhibitor resistant cell lines. This first in human study demonstrates that sirolimus therapy is associated with elevation in PCSK9 levels which is not associated with sirolimus-induced hypercholesterolemia.