Heparin-binding EGF-like growth factor (HB-EGF) antisense oligonucleotide protected against hyperlipidemia-associated atherosclerosis

Background and aims

Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.     

PACAP deficiency aggravates atherosclerosis in ApoE deficient mice

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) plays an important role in cytoprotection, inflammation and cardiovascular regulation. Thus, we studied the involvement of PACAP in atherogenesis. Differentiated human THP-1 macrophages (MΦ) were stimulated with oxidized low-density lipoproteins (oxLDL) and the influence of PACAP38 treatment on lipid content and TNF release was determined. To test the effect of PACAP deficiency (PACAP^?/?) on the development of atherosclerosis under standard chow (SC) or cholesterol-enriched diet (CED) in vivo, PACAP^?/? mice were crossbred with ApoE^?/? to generate PACAP^?/?/ApoE^?/? mice. Blood cholesterol and triglyceride levels were quantified. Lumen stenosis in the brachiocephalic trunk, cellularity and amounts of pro-inflammatory as well as autophagy-, apoptosis- and necroptosis-relevant proteins were analysed in atherosclerotic plaques by quantitative immunohistochemistry. In vitro, PACAP38 inhibited oxLDL-induced intracellular lipid storage as well as TNF release in MФ. In vivo, after SC, but not under CED, PACAP^?/?/ApoE^?/? mice showed an increased lumen stenosis compared to ApoE^?/? mice. In atherosclerotic plaques of PACAP^?/?/ApoE^?/? mice, the immunoreactive areas of TNF⁺, IL-1β⁺, autophagic, apoptotic and necroptotic cells were increased. In contrast, the overall cell density was decreased compared to ApoE^?/? under SC, while no differences were seen under CED. Similar plasma cholesterol levels were observed in PACAP^?/?/ApoE^?/? and ApoE^?/? mice under the respective feeding regime. Thus, PACAP^?/-/ApoE^?/? mice represent a novel mouse model of accelerated atherosclerosis where CED is not required. Our data indicate that PACAP acts as an endogenous atheroprotective neuropeptide. Thus, stable PACAP agonists may have potential as anti-atherosclerotic therapeutics. The specific PACAP receptor(s) mediating atheroprotection remain(s) to be identified.     

血糖、血脂水平与糖尿病视网膜病变患者视力损害的相关性研究

目的探讨血糖、血脂水平与糖尿病视网膜病变患者视力损害的相关性。方法选取2016年1月至2018年1月我院内分泌科收治的250例DR患者进行研究。根据视力分级标准分为三个组:盲组(n=28),低视力组(n=80),低视力以上组(n=142)。比较各组患者FPG、HbAlC、TC、TG、LDL-C、HDL-C、LDL-C/HDL-C、ApoB、ApoA1、ApoB/ApoA1水平,对FPG、HbA1C、LDL-C/HDL-C及ApoB/ApoA1与DR患者视力损害进行Pearman相关性分析和Logistic回归分析。结果三组患者的TC、TG差异均无统计学意义(P>0.05);与低视力以上组相比,盲组和低视力组FPG、HbAlC、LDL-C、LDL-C/HDL-C、ApoB、ApoB/ApoA1更高,HDL-C、ApoA1更低(P<0.05);盲组FPG、HbAlC、LDL-C、LDL-C/HDL-C、ApoB、ApoB/ApoAl显著高于低视力组,HDL-C、ApoA1显著低于低视力组(P<0. 05)。经Spearman相关性分析,FPG、HbAlC、LDL-C/HDL-C、ApoB/ApoA1比值与DR患者视力损害均呈正相关。经Logistic回归分析,FPG、HbAlC、LDL-C/HDL-C、ApoB/ApoA1均是DR患者视力损害的独立危险因素。结论 FPG、HbAlC、LDL-C/HDL-C、ApoB/ApoA1与DR患者的视力损害有密切关系,通过监测这些指标有利于DR患者视力损害的预测,及时采取治疗措施。