Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
Versiti Blood Research Institute, Milwaukee, WI 53226, USA.
Rev Cardiovasc Med. 2021 Mar 30;22(1):67-81. doi: 10.31083/j.rcm.2021.01.256.
The risks for adverse thrombotic events, including myocardial infarction, stroke, and deep vein thrombosis, are markedly increased in dyslipidemia and other metabolic disorders and are the major cause of death worldwide. Recent evidence points out that increased thrombotic risk in dyslipidemia is mediated by platelets circulating in a pre-activated state. The mechanisms of platelet reactivity in this setting are multifaceted including platelet activation by classic agonist receptor signaling as well as platelet sensitization by pattern recognition receptors. Elevated platelet counts in dyslipidemia due to dysregulation in hematopoiesis also contribute to the overall thrombotic phenotype. Despite recent advancements in antiplatelet and anticoagulation therapies, recurrences of adverse thrombotic events remain to be a large clinical burden. In the light of new knowledge, understanding mechanisms that drive pathologic thrombosis in dyslipidemia, the antithrombotic approach shall be revisited. Here, we discuss potential therapeutic avenues based on the overview of platelet signaling mechanisms that contribute to a prothrombotic phenotype in dyslipidemia.
脂代谢紊乱和其他代谢紊乱会显著增加不良血栓事件（包括心肌梗死、中风和深静脉血栓形成）的风险，是全球主要的死亡原因。最近的证据表明，脂代谢紊乱中增加的血栓形成风险是由处于预激活状态的循环血小板介导的。在这种情况下，血小板反应性的机制是多方面的，包括经典激动剂受体信号诱导的血小板激活以及模式识别受体引起的血小板致敏。由于造血失调导致的脂代谢紊乱中血小板计数升高也导致了整体血栓表型。尽管抗血小板和抗凝治疗最近取得了进展，但不良血栓事件的复发仍然是一个巨大的临床负担。鉴于新知识，为了了解脂代谢紊乱中导致病理性血栓形成的机制，抗血栓治疗方法需要重新评估。在这里，我们根据导致脂代谢紊乱中促血栓形成表型的血小板信号转导机制的概述，讨论潜在的治疗途径。
