Apelin, an essential mediator of homeostasis, is crucially involved in cardiovascular diseases, including ischemic stroke. However, the functional roles of apelin-17 in cerebral collateral circulation and ischemic stroke protection are unknown. Here, we investigated the association between plasma apelin-17 levels and collateral circulation in patients with ischemic stroke and examined the mechanism undergirding the effects of apelin-17 on cerebral artery contraction and ischemic stroke protection in an animal model. Plasma nitric oxide (NO), apelin-17, and apelin-36 levels were assessed by enzyme-linked immunosorbent assays in ischemic stroke patients with good or poor collateral circulation and in healthy participants. Additionally, the effects of apelin-17 on rat basilar artery contractions (in vitro) and cerebral ischemia (in vivo) were determined using vessel tension measurements and nuclear magnetic resonance, respectively. Patients with good collateral circulation had significantly higher plasma apelin-17 and apelin-36 levels than both patients with poor collateral circulation and healthy participants and plasma NO levels significantly higher than those in healthy participants. In vitro, apelin-17 pretreatment markedly attenuated U46619-induced rat basilar artery contractions in an endothelium-dependent manner. Additionally, NO production or guanylyl cyclase inhibitors abolished the apelin-17 effect on U46619-induced vascular contraction. Intravenous pretreatment of rats with apelin-17 markedly reduced cerebral infarct volume at 24 h after middle cerebral artery occlusion. Plasma apelin-17 levels in ischemic stroke patients were positively associated with enhanced collateral circulation, which our animal study data suggested may have resulted from an apelin-17-induced cerebral artery dilation mediated through the NO-cGMP pathway.
Patients with moyamoya disease (MMD) or intracranial atherosclerotic disease (ICAD) experience similar cerebral ischaemic events. However, MMD patients show greater angiogenesis and arteriogenesis, which play crucial roles in collateral circulation development to enhance clinical prognosis and outcome. Apelins have been associated with angiogenesis and arteriogenesis. Therefore, the aim of the present study was to determine whether apelin levels were higher in patients with MMD than in patients with ICAD or in healthy controls. We compared plasma apelin levels in 29 patients with MMD, 82 patients with ICAD, and 25 healthy participants. Twelve-hour fasting blood samples were collected and analysed using commercially available kits. Univariate analyses indicated that compared with the ICAD and healthy control groups, the MMD group had higher apelin-12, apelin-13, apelin-36, and nitric oxide levels. Binary logistic regression analyses further showed that the plasma apelin-12 level was substantially higher in MMD patients than in ICAD patients. Patients with MMD were also differentiated from patients with ICAD by their mean ages, with the former being younger. Therefore, the plasma apelin-12 level is a potential diagnostic marker for differentiating MMD and ICAD and may provide a treatment strategy for enhancing collateral circulation development and clinical prognosis and outcome.
ObjectiveAn HLA imputation was conducted to explore the relationship between HLA and patients with moyamoya disease (MMD) in the Chinese Han population.MethodsIn this study, we performed an association analysis of the major histocompatibility complex region in 2,786 individuals of Chinese Han ancestry (2,031 controls and 755 patients with MMD), through a widely used HLA imputation method.ResultsWe identified that the variant rs3129731 (odds ratio [OR] = 1.79, p = 3.69 × 10−16) located between the MTCO3P1 and HLA-DQA2 is a major genetic risk factor for MMD. In addition to this variant, found in the conditional association analysis, we also detected another independent signal, rs1071817 (OR = 0.62, p = 1.20 × 10−11), in HLA-B.ConclusionsOur research suggests that the genetic polymorphism of HLA-DQA2 and HLA-B could be a genetic predisposing factor for MMD in Chinese Han. This may provide some evidence for further HLA-related studies of patients with MMD of Chinese Han ethnicity and indicates that MMD is an immune-related disease.
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