微血管结构和功能改变是阻碍血流流速、形成高血压的主要原因。MPO和apoE是HDL和LDL结合的蛋白。HDL和LDL从血浆跨过内皮进入外周微血管的细胞间液，导致MPO和apoE与微血管细胞相互作用。MPO的氧化作用改变微血管结构和功能，MPO水平增加与舒张压正关联，MPO水平降低与血压降低相关。涉及Cys残基错义突变的APOE基因多态性决定不同个体apoE抗氧化能力强弱，但是不同个体apoE被氧化状态由MPO氧化能力决定。我们前期研究发现：高血压合并动脉粥样硬化患者血清MPO过氧化体系与LDL的活性醛基渐进性修饰增强相关；APOE基因中突变成无抗氧化能力氨基酸残基的基因多态性位点可能是高血压的危险因素。基于MPO的氧化能力与apoE的抗氧化能力的直接对抗关系，本项目旨在研究HDL和LDL所结合MPO的氧化能力与涉及Cys残基错义突变的APOE基因多态性的交互作用与高血压严重程度的关联和机制

Myeloperoxidase (MPO) and apolipoprotein E (apoE) are high-density-lipoprotein–binding and low-density-lipoprotein–binding proteins. LDL and HDL transfer from plasma into interstitial fluid across the peripheral vascular endothelium via passive ultrafiltration in humans, reflecting that MPO and apoE interact with microvascular cells. MPO oxidation leads to the changes in microvascular structure and function, conferring hypertension process. Notably, there are two cysteine (Cys)-correlating missense mutations in APOE polymorphisms (rs429358 and rs7412). Cys is susceptible to oxidation to give the disulfide derivative cystine, serving as an important structural and anti-oxidative role. ApoE restricts MPO oxidation, and there are differences in the antioxidant capacity and oxidized state of apoE in different individuals. Our previous investigations indicated that ⑴ the shift from the reaction system of paraoxonase 1 to the peroxidation reaction system of MPO correlates with atherosclerosis; ⑵ the peroxidation reaction system of MPO correlated with progressive LDL modifications via reactive aldehydes in atherosclerotic patients with hypertension; and ⑶ APOE genotypes (ε2/ε2 and ε2/ε3) showed a possible association with hypertension, and APOE genotypes (ε3/ε4 and ε4/ε4) had a 2.08-fold risk of developing hypertension. Based on substantial confrontation between MPO oxidation and apoE anti-oxidation, we shall investigate the contribution of interactions between the oxidative capacity of MPO and APOE polymorphism involved in cysteine-missense mutations to the severity of hypertension.