Department of Pediatrics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Curr Atheroscler Rep. 2022 Jan;24(1):1-12. doi: 10.1007/s11883-022-00979-y. Epub 2022 Feb 2.
The accumulation of triglyceride-rich lipoproteins (TRLs) in plasma in patients with familial chylomicronaemia syndrome (FCS) or severe hypertriglyceridemia is associated with an increased risk of potentially life-threatening pancreatitis. Elevated TRL levels have also been suggested to contribute to atherosclerotic cardiovascular disease (ASCVD). This review provides the latest progress that has been made in this field of research.
Apolipoprotein C-III and angiopoietin-like protein 3 play key roles in the metabolism of TRLs. Targeting their production in the liver or their presence in the circulation effectively reduces triglycerides in patients with FCS or severe hypertriglyceridemia. Attempts to reduce triglyceride synthesis in the small intestine have been halted. Early studies with a fibroblast growth factor 21 agonist have shown to reduce plasma triglycerides and hepatic steatosis and improve glucose homeostasis. New drugs have recently been shown to effectively reduce plasma triglycerides which render hope for treating the risk of pancreatitis. Studies that have just been initiated will learn whether this unmet clinical will be met. It is too early to evaluate the potential of these drugs to reduce the risk of atherosclerosis through the reduction of triglycerides.
目的综述：家族性乳糜微粒血症综合征（FCS）或严重高甘油三酯血症患者血浆中富含甘油三酯的脂蛋白（TRLs）的积累与潜在威胁生命的胰腺炎风险增加相关。升高的 TRL 水平也被认为与动脉粥样硬化性心血管疾病（ASCVD）有关。这篇综述提供了该研究领域的最新进展。
最新发现：载脂蛋白 C-III 和血管生成素样蛋白 3 在 TRL 的代谢中发挥关键作用。靶向肝脏产生或循环中存在的载脂蛋白 C-III 和血管生成素样蛋白 3 可有效降低 FCS 或严重高甘油三酯血症患者的甘油三酯。减少小肠甘油三酯合成的尝试已经停止。早期的成纤维细胞生长因子 21 激动剂研究表明，它可以降低血浆甘油三酯和肝脂肪变性，改善葡萄糖稳态。最近的研究表明，新的药物可以有效地降低血浆甘油三酯，这为治疗胰腺炎风险带来了希望。刚刚开始的研究将了解这种未满足的临床需求是否能够得到满足。评估这些药物通过降低甘油三酯降低动脉粥样硬化风险的潜力还为时过早。
