Department of Internal Medicine II, University Hospital Bonn, University of Bonn, Germany.
Arterioscler Thromb Vasc Biol. 2022 Oct;42(10):1220-1228. doi: 10.1161/ATVBAHA.122.318048. Epub 2022 Aug 25.
Growing evidence suggests that ceramides play an important role in the development of atherosclerotic and valvular heart disease. Ceramides are biologically active sphingolipids that are produced by a complex network of enzymes. Lowering cellular and tissue levels of ceramide by inhibiting the ceramide-producing enzymes counteracts atherosclerotic and valvular heart disease development in animal models. In vascular tissues, ceramides are produced in response to hyperglycemia and TNF (tumor necrosis factor)-α signaling and are involved in NO-signaling and inflammation. In humans, elevated blood ceramide levels are associated with cardiovascular events. Furthermore, important cardiovascular risk factors, such as obesity and diabetes, have been linked to ceramide accumulation. This review summarizes the basic mechanisms of how ceramides drive cardiovascular disease locally and links these findings to the intriguing results of human studies on ceramides as biomarkers for cardiovascular events. Moreover, we discuss the current state of interventions to therapeutically influence vascular ceramide metabolism, both locally and systemically.
越来越多的证据表明，神经酰胺在动脉粥样硬化性和瓣膜性心脏病的发展中起着重要作用。神经酰胺是一种生物活性的鞘脂类，由一个复杂的酶网络产生。通过抑制神经酰胺产生酶来降低细胞和组织中的神经酰胺水平，可以在动物模型中对抗动脉粥样硬化性和瓣膜性心脏病的发展。在血管组织中，神经酰胺是对高血糖和 TNF（肿瘤坏死因子）-α信号的反应而产生的，并且参与了 NO 信号和炎症。在人类中，血液神经酰胺水平升高与心血管事件有关。此外，重要的心血管危险因素，如肥胖和糖尿病，与神经酰胺积累有关。这篇综述总结了神经酰胺如何在局部驱动心血管疾病的基本机制，并将这些发现与人类研究中关于神经酰胺作为心血管事件生物标志物的有趣结果联系起来。此外，我们还讨论了目前局部和全身治疗性干预来影响血管神经酰胺代谢的情况。
