Luquero Aureli, Badimon Lina, Borrell-Pages Maria
Cardiovascular Program ICCC, IR-Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.
Centro de Investigación en Red- Área Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain.
Front Cardiovasc Med. 2021 Mar 23;8:639727. doi: 10.3389/fcvm.2021.639727. eCollection 2021.
The relevance of PCSK9 in atherosclerosis progression is demonstrated by the benefits observed in patients that have followed PCSK9-targeted therapies. The impact of these therapies is attributed to the plasma lipid-lowering effect induced when LDLR hepatic expression levels are recovered after the suppression of soluble PCSK9. Different studies show that PCSK9 is involved in other mechanisms that take place at different stages during atherosclerosis development. Indeed, PCSK9 regulates the expression of key receptors expressed in macrophages that contribute to lipid-loading, foam cell formation and atherosclerotic plaque formation. PCSK9 is also a regulator of vascular inflammation and its expression correlates with pro-inflammatory cytokines release, inflammatory cell recruitment and plaque destabilization. Furthermore, anti-PCSK9 approaches have demonstrated that by inhibiting PCSK9 activity, the progression of atherosclerotic disease is diminished. PCSK9 also modulates thrombosis by modifying platelets steady-state, leukocyte recruitment and clot formation. In this review we evaluate recent findings on PCSK9 functions in cardiovascular diseases beyond LDL-cholesterol plasma levels regulation.
在接受PCSK9靶向治疗的患者中观察到的益处证明了PCSK9在动脉粥样硬化进展中的相关性。这些治疗的效果归因于可溶性PCSK9被抑制后，肝脏LDLR表达水平恢复时所诱导的血浆降脂作用。不同的研究表明，PCSK9参与了动脉粥样硬化发展不同阶段发生的其他机制。事实上，PCSK9调节巨噬细胞中关键受体的表达，这些受体有助于脂质负载、泡沫细胞形成和动脉粥样硬化斑块形成。PCSK9也是血管炎症的调节因子，其表达与促炎细胞因子释放、炎症细胞募集和斑块不稳定相关。此外，抗PCSK9方法已经证明，通过抑制PCSK9活性，可以减少动脉粥样硬化疾病的进展。PCSK9还通过改变血小板稳态、白细胞募集和血栓形成来调节血栓形成。在这篇综述中，我们评估了关于PCSK9在心血管疾病中功能的最新发现，这些功能超出了对血浆低密度脂蛋白胆固醇水平的调节。
