1st Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece.
Int J Cardiol. 2011 Mar 17;147(3):349-58. doi: 10.1016/j.ijcard.2010.08.009. Epub 2010 Sep 9.
Familial hypercholesterolemia (FH) is a common autosomal disorder associated with hypercholesterolemia which usually results from a mutation in the coding region of the low density lipoprotein (LDL) receptor (R) activity. Only 20% of untreated heterozygote (h) FH men reach 70 years of age. Therefore, the diagnosis of hFH is a better predictor of coronary heart disease than risk-based algorithms. Fasting and postprandial hypertriglyceridemia are also considered as risk factors for atherosclerosis. The plasma triglycerides (TG)s are formed from two major sources; intestinally-derived chylomicrons and hepatically-derived very low density lipoproteins (VLDL). Potentially, atherogenic remnants of TG-rich lipoproteins accumulate in the postprandial state. In addition, TG-rich lipoproteins may promote the formation of atherogenic small dense LDL. In FH subjects, lipoprotein metabolism seems to be impaired and may contribute to premature atherosclerosis. This was documented in many studies in which mice lacking LDLR present hypercholesterolemia, increased plasma TG-rich lipoprotein remnants and develop premature spontaneous atherosclerosis. In this review, we focus on the current knowledge regarding TG metabolism on a selected clinically condition such as FH. Variation in clinical characteristics has been described between studies which may occur due to dissimilarity in the molecular defect of FH. Additionally, the relationship between TG levels in FH subjects and the development of atherosclerosis, as well as the appropriate treatment for these patients is analysed.
家族性高胆固醇血症(FH)是一种常见的常染色体疾病,与高胆固醇血症有关,通常是由于低密度脂蛋白(LDL)受体(R)活性的编码区域的突变引起的。未经治疗的杂合子(h)FH 男性中只有 20%能活到 70 岁。因此,hFH 的诊断比基于风险的算法更能预测冠心病。空腹和餐后高甘油三酯血症也被认为是动脉粥样硬化的危险因素。血浆甘油三酯(TG)主要来源于两个来源;肠源性乳糜微粒和肝源性极低密度脂蛋白(VLDL)。在餐后状态下,富含 TG 的脂蛋白的致动脉粥样硬化残基可能会积累。此外,富含 TG 的脂蛋白可能会促进致动脉粥样硬化的小而密 LDL 的形成。在 FH 患者中,脂蛋白代谢似乎受损,可能导致动脉粥样硬化提前发生。这在许多研究中都有记录,在这些研究中,缺乏 LDLR 的小鼠会出现高胆固醇血症、血浆 TG 丰富的脂蛋白残基增加,并提前自发发生动脉粥样硬化。在这篇综述中,我们关注了在 FH 等特定临床条件下关于 TG 代谢的最新知识。研究之间的临床特征变化可能是由于 FH 的分子缺陷不同而导致的。此外,还分析了 FH 患者的 TG 水平与动脉粥样硬化发展之间的关系,以及这些患者的适当治疗方法。