Simonelli Sara, Tinti Cristina, Salvini Laura, Tinti Laura, Ossoli Alice, Vitali Cecilia, Sousa Vitor, Orsini Gaetano, Nolli Maria Luisa, Franceschini Guido, Calabresi Laura
Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
Biologicals. 2013 Nov;41(6):446-9. doi: 10.1016/j.biologicals.2013.09.007. Epub 2013 Oct 18.
Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. Mutations in the LCAT gene leads to two rare disorders, familial LCAT deficiency and fish-eye disease, both characterized by severe hypoalphalipoproteinemia associated with several lipoprotein abnormalities. No specific treatment is presently available for genetic LCAT deficiency. In the present study, recombinant human LCAT was expressed and tested for its ability to correct the lipoprotein profile in LCAT deficient plasma. The results show that rhLCAT efficiently reduces the amount of unesterified cholesterol (-30%) and promotes the production of plasma cholesteryl esters (+210%) in LCAT deficient plasma. rhLCAT induces a marked increase in HDL-C levels (+89%) and induces the maturation of small preβ-HDL into alpha-migrating particles. Moreover, the abnormal phospholipid-rich particles migrating in the LDL region were converted in normally sized LDL.
卵磷脂胆固醇酰基转移酶（LCAT）是负责血浆中胆固醇酯化的酶。LCAT基因突变会导致两种罕见疾病，即家族性LCAT缺乏症和鱼眼病，两者均以严重的低α脂蛋白血症为特征，并伴有多种脂蛋白异常。目前尚无针对遗传性LCAT缺乏症的特异性治疗方法。在本研究中，表达了重组人LCAT，并测试了其纠正LCAT缺乏血浆中脂蛋白谱的能力。结果表明，重组人LCAT能有效降低LCAT缺乏血浆中未酯化胆固醇的含量（降低30%），并促进血浆胆固醇酯的生成（增加210%）。重组人LCAT可使高密度脂蛋白胆固醇（HDL-C）水平显著升高（升高89%），并促使小的前β-HDL成熟为α迁移颗粒。此外，在低密度脂蛋白（LDL）区域迁移的富含异常磷脂的颗粒转变为正常大小的LDL。
