Myoglobinemia, Peripheral Arterial Disease, and Patient Mortality.
Myoglobinemia, Peripheral Arterial Disease, and Patient Mortality.
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DOI：
10.1097/xcs.0000000000000554
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发表时间：
2023-04-01
影响因子：
5.2
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中科院分区：
文献类型：
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外周动脉疾病(PAD)由于血流灌注不足而导致腿部肌肉损伤，并使心血管事件和死亡率增加2-3倍。目前尚不清楚PAD是高危心血管疾病的生物标志物，还是骨骼肌损伤损害动脉健康。这项工作的目的是测试血清肌红蛋白水平(肌红蛋白血症)是否是PAD的标志，如果是，肌红蛋白是否损害血管健康。患者的血液样本来自PAD和对照组(无PAD)患者，并询问肌红蛋白浓度和一氧化氮的生物利用度。随着时间的推移，患者死亡率从医疗记录中记录下来。测定血管内皮细胞肌红蛋白活性和动脉功能。肌红蛋白是症状性PAD的生物标志物，与一氧化氮的生物利用度呈负相关；200 ng/mL肌红蛋白在体外可增加血管内皮细胞的通透性，降低硝酸盐的生物利用度。在体外，100 ng/mL肌红蛋白使幼鼠主动脉的血管张力增加约1.5倍，损害绝对血管松弛。在活体实验中，我们证明了肌红蛋白血症导致猪的血流介导的收缩功能受损。肌红蛋白水平在100 ng/m L或更高的患者的死亡率显著高于肌红蛋白水平低于100 ng/m L的患者。结合患者数据，体外、体外和体内测试，我们发现肌红蛋白是症状性PAD的生物标记物和动脉健康的有效调节因子，可以增加血管张力，增加血管通透性，并导致内皮功能障碍，所有这些都可能导致PAD患者对心血管事件和死亡的易感性。外周动脉疾病(PAD)导致肌肉损伤，并与心血管事件和死亡率增加2×至3倍相关。PAD是一个生物标记物，还是它有PAD的生物成分对这些事件起作用？这项工作将肌红蛋白作为对动脉健康有生物学影响的症状性PAD的生物标志物。
Peripheral arterial disease (PAD) causes leg muscle damage due to inadequate perfusion and increases cardiovascular events and mortality 2- to 3-fold. It is unclear if PAD is a biomarker for high-risk cardiovascular disease or if skeletal muscle injury harms arterial health. The objective of this work is to test if serum myoglobin levels (myoglobinemia) are a marker of PAD, and if so, whether myoglobin impairs vascular health. Patient blood samples were collected from PAD and control (no PAD) patients and interrogated for myoglobin concentrations and nitric oxide bioavailability. Patient mortality over time was captured from the medical record. Myoglobin activity was tested on endothelial cells and arterial function. Myoglobin is a biomarker for symptomatic PAD and was inversely related to nitric oxide bioavailability; 200 ng/mL myoglobin in vitro increased endothelial cell permeability in vitro and decreased nitrate bioavailability. Ex vivo, 100 ng/mL myoglobin increased vascular tone in naive murine aortas approximately 1.5 times, impairing absolute vessel relaxation. In vivo, we demonstrated that myoglobinemia caused impaired flow-mediated dilation in a porcine model. Patients presenting with myoglobin levels of 100 ng/mL or greater had significantly more deaths than those with myoglobin levels of less than 100 ng/mL. Using a combination of patient data, in vitro, ex vivo, and in vivo testing, we found that myoglobin is a biomarker for symptomatic PAD and a potent regulator of arterial health that can increase vascular tone, increase vascular permeability, and cause endothelial dysfunction, all of which may contribute to the vulnerability of PAD patients to cardiovascular events and death. Peripheral arterial disease (PAD) causes muscle damage and is associated with a 2× to 3× increase in cardiovascular events and mortality. Is PAD a biomarker or does it have a biologic component of PAD contributing to these events? This work presents myoglobin as a biomarker for symptomatic PAD with biologic impact on arterial health.