Section of Inflammation and Cardiometabolic Diseases, Cardiovascular Branch.
Proteomics Core, and.
JCI Insight. 2023 Oct 23;8(20):e172893. doi: 10.1172/jci.insight.172893.
Oxidized apolipoprotein B (oxLDL) and oxidized ApoA-I (oxHDL) are proatherogenic. Their prognostic value for assessing high-risk plaques by coronary computed tomography angiography (CCTA) is missing.
In a prospective, observational study, 306 participants with cardiovascular disease (CVD) had extensive lipoprotein profiling. Proteomics analysis was performed on isolated oxHDL, and atherosclerotic plaque assessment was accomplished by quantitative CCTA.
Patients were predominantly White, overweight men (58.5%) on statin therapy (43.5%). Increase in LDL-C, ApoB, small dense LDL-C (P < 0.001 for all), triglycerides (P = 0.03), and lower HDL function were observed in the high oxLDL group. High oxLDL associated with necrotic burden (NB; β = 0.20; P < 0.0001) and fibrofatty burden (FFB; β = 0.15; P = 0.001) after multivariate adjustment. Low oxHDL had a significant reverse association with these plaque characteristics. Plasma oxHDL levels better predicted NB and FFB after adjustment (OR, 2.22; 95% CI, 1.27-3.88, and OR, 2.80; 95% CI, 1.71-4.58) compared with oxLDL and HDL-C. Interestingly, oxHDL associated with fibrous burden (FB) change over 3.3 years (β = 0.535; P = 0.033) when compared with oxLDL. Combined Met136 mono-oxidation and Trp132 dioxidation of HDL showed evident association with coronary artery calcium score (r = 0.786; P < 0.001) and FB (r = 0.539; P = 0.012) in high oxHDL, whereas Met136 mono-oxidation significantly associated with vulnerable plaque in low oxHDL.
Our findings suggest that the investigated oxidized lipids are associated with high-risk coronary plaque features and progression over time in patients with CVD.
gov NCT01621594.
National Heart, Lung, and Blood Institute at the NIH Intramural Research Program.
氧化载脂蛋白 B（oxLDL）和氧化载脂蛋白 A-I（oxHDL）具有动脉粥样硬化作用。它们在通过冠状动脉计算机断层扫描血管造影术（CCTA）评估高危斑块方面的预后价值尚不清楚。
在一项前瞻性、观察性研究中，306 名患有心血管疾病（CVD）的患者进行了广泛的脂蛋白分析。对分离的 oxHDL 进行蛋白质组学分析，并通过定量 CCTA 评估动脉粥样硬化斑块。
患者主要为白种人、超重男性（58.5%），服用他汀类药物（43.5%）。高 oxLDL 组的 LDL-C、ApoB、小而密 LDL-C（均 P<0.001）、甘油三酯（P=0.03）升高，HDL 功能降低。多元调整后，高 oxLDL 与坏死负荷（NB；β=0.20；P<0.0001）和纤维脂肪负荷（FFB；β=0.15；P=0.001）相关。低 oxHDL 与这些斑块特征有显著的反向关联。与 oxLDL 和 HDL-C 相比，调整后血浆 oxHDL 水平更好地预测 NB 和 FFB（OR，2.22；95%CI，1.27-3.88，和 OR，2.80；95%CI，1.71-4.58）。有趣的是，与 oxLDL 相比，oxHDL 与 3.3 年内纤维（FB）变化相关（β=0.535；P=0.033）。在高 oxHDL 中，HDL 的 Met136 单氧化和 Trp132 二氧化与冠状动脉钙评分（r=0.786；P<0.001）和 FB（r=0.539；P=0.012）有明显关联，而低 oxHDL 中 Met136 单氧化与易损斑块显著相关。
我们的研究结果表明，在所研究的氧化脂质与 CVD 患者的高危冠状动脉斑块特征和随时间的进展有关。
gov NCT01621594。
美国国立卫生研究院（NIH）内部研究计划的国家心肺血液研究所。
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