Centro Cardiologico Monzino IRCCS, Milano, Italy.
Cardiovascular Tissue Bank of Milan, Centro Cardiologico Monzino IRCCS, Milano, Italy.
Commun Biol. 2021 Sep 21;4(1):1109. doi: 10.1038/s42003-021-02630-z.
The research into the pathophysiology of atherosclerosis has considerably increased our understanding of the disease complexity, but still many questions remain unanswered, both mechanistically and pharmacologically. Here, we provided evidence that the pro-oxidant enzyme Prenylcysteine Oxidase 1 (PCYOX1), in the human atherosclerotic lesions, is both synthesized locally and transported within the subintimal space by proatherogenic lipoproteins accumulating in the arterial wall during atherogenesis. Further, Pcyox1 deficiency in Apoe mice retards atheroprogression, is associated with decreased features of lesion vulnerability and lower levels of lipid peroxidation, reduces plasma lipid levels and inflammation. PCYOX1 silencing in vitro affects the cellular proteome by influencing multiple functions related to inflammation, oxidative stress, and platelet adhesion. Collectively, these findings identify the pro-oxidant enzyme PCYOX1 as an emerging player in atherogenesis and, therefore, understanding the biology and mechanisms of all functions of this unique enzyme is likely to provide additional therapeutic opportunities in addressing atherosclerosis.
对动脉粥样硬化病理生理学的研究极大地提高了我们对疾病复杂性的理解，但在机制和药理学方面仍有许多问题尚未得到解答。在这里，我们提供的证据表明，在人类动脉粥样硬化病变中，前氧化酶 Prenylcysteine Oxidase 1（PCYOX1）在动脉壁中积累的促动脉粥样硬化脂蛋白在动脉粥样硬化形成过程中，不仅在局部合成，而且在 subintimal 空间内运输。此外，Apoe 小鼠中的 Pcyox1 缺乏会减缓动脉粥样硬化进展，与病变易损性特征降低和脂质过氧化水平降低相关，降低血浆脂质水平和炎症。体外的 PCYOX1 沉默通过影响与炎症、氧化应激和血小板黏附相关的多种功能来影响细胞蛋白质组。总的来说，这些发现将促氧化酶 PCYOX1 确定为动脉粥样硬化形成过程中的一个新出现的参与者，因此，了解这种独特酶的所有功能的生物学和机制可能会为解决动脉粥样硬化提供更多的治疗机会。
