Functions of the endothelium and its role in hematopoietic cell transplantation

The endothelium is a single-layered structure that responds to physical and chemical signals with various factors it synthesizes. In the early days of its discovery, as the inner wall of the vessels, the endothelium was thought to be a simple barrier that lays on the surface. Over time it is discovered that endothelium maintains body homeostasis with the molecules it synthesizes, despite its simple single-layer structure. It has been accepted as an important organ that contributes to the maintenance of vascular tone, cell adhesion, inflammation, vascular permeability and coagulation. Any imbalance in these physiological and pathological events causes endothelial dysfunction. This can cause many diseases such as atherosclerosis, hypertension, diabetes, or it can occur because of these. Endothelial related disorders may also complicate hematopoietic stem cell transplantation (HSCT), which is used to treat various hematologic and neoplastic diseases. These life-threatening complications include graft-versus-host disease, hepatic veno-occlussive disease, transplant-associated thrombotic microangiopathy and diffuse alveolar hemorrhage. They share a similar pathophysiology involving endothelial cells with different clinical presentations. Therefore, current researche on the issue is putting the endothelium under the spotlight for novel markers and treatment options that should be used to monitor or treat at least some of these complications following HSCT.     

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.     

小颗粒致密低密度脂蛋白氧化特性及对血管内皮细胞脂质过氧化的影响

了解小颗粒致密低密度脂蛋白中抗氧化维生素含量、氧化特性 ,探讨其对血管内皮细胞脂质过氧化的影响。采用二次密度梯度超速离心的方法分离制备小颗粒致密低密度脂蛋白 ,高压液相色谱测定其抗氧化物质维生素A、E和 β 胡萝卜素 ;连续监测小颗粒致密低密度脂蛋白在 2 34nm的吸光度以测定其氧化敏感曲线 ;在血管内皮培养液中分别加入不同浓度的小颗粒致密低密度脂蛋白 ,培养后测定培养液丙二醛的浓度。实验成功分离小颗粒致密低密度脂蛋白 ,与大而轻低密度脂蛋白相比 ,维生素A、E和 β 胡萝卜素等抗氧化物质及总抗氧化能力明显减少 ,只有大而轻低密度脂蛋白的 6 5 %、39%和 2 4 % ,故小颗粒致密低密度脂蛋白氧化的延迟时间只有大而轻低密度脂蛋白的 37.5 % ,但硫代巴比妥酸反应物质值及氧化速率分别是大而轻低密度脂蛋白的 1 .7倍和 1 .2 8倍 ;培养液中丙二醛含量随加入脂蛋白的浓度和作用时间而增高 ,2 4h时小颗粒致密低密度脂蛋白 5 0mg组、1 0 0mg组、1 5 0mg组与相同剂量大而轻低密度脂蛋白组比较丙二醛显著增高 (P <0 .0 5 )。上述结果提示 :小颗粒致密低密度脂蛋白中抗氧化物质及抗氧化能力下降 ,氧化敏感性增高 ,并促进内皮细胞过氧化损伤     

脂蛋白脂酶Hind Ⅲ基因多态性与动脉硬化性脑梗死的关系

目的研究脂蛋白脂酶HindⅢ基因多态性与动脉硬化性脑梗死发病的关系及其对血脂、颈动脉斑块的影响。方法选择166例动脉硬化性脑梗死患者，采用聚合酶链反应-限制性片段长度多态性分析检测脂蛋白脂酶的HindⅢ基因多态性，颈动脉超声多普勒检查颈总动脉内膜中层厚度和颈动脉斑块，并与72名健康对照比较。结果在脑梗死组中H＋H＋基因型频率和H＋等位基因频率明显高于对照组（OR=2．267，P=0．004；OR=1．903，P=0．004），而血脂水平、颈总动脉内膜中层厚度、颈动脉斑块分级与对照组比较差异无统计学意义。结论脂蛋白脂酶的HindⅢ基因多态性与脑梗死的关系密切，H＋H＋基因型可能是脑梗死的危险因素。     

种植受体血管内皮细胞在异种血管移植中的实验研究

目的　探讨种植受体血管内皮细胞在抗异种血管移植超急排斥反应 (HAR)方面的意义。方法　选用豚鼠→大鼠移植模型 ,先将分离、培养的大鼠动脉内皮细胞种植于去内皮的豚鼠动脉内壁 ,再将此豚鼠动脉植入大鼠体内 ,观察动脉血栓形成时间 ,并采用免疫组化技术检测了 Ig M、C3在移植后豚鼠动脉壁上沉积的情况。结果　已种植大鼠内皮细胞的豚鼠动脉血栓形成时间 (2 0 .3± 4.42 h)较植入大鼠体内的正常豚鼠动脉 (0 .35± 0 .2 84h)以及单纯去内皮豚鼠动脉血栓形成时间 (0 .16 5± 0 .0 77h)显著延长 (P<0 .0 0 1)。免疫组化结果显示 ,植入大鼠体内的正常豚鼠内皮细胞表面有 Ig M和 C3沉积 ,而预先种植大鼠内皮细胞的豚鼠动脉内壁无 Ig M和 C3沉积。结论　在异种供体血管壁上预先种植受者血管内皮细胞 ,可延长移植的异种供体血管通畅时间 ,该技术可能在抗异种血管移植 HAR方面具有重要意义     

增生性瘢痕中血管内皮细胞生物学功能的研究

目的 探讨增生性瘢痕中血管内皮细胞的生物学功能及其与瘢痕形成的关系。方法 取人增生性瘢痕组织和正常皮肤组织，进行组织学观察。分离和纯化2种标本中的血管内皮细胞，应用酶联免疫吸附测定法分别检测单个血管内皮细胞中转化生长因子β1，（TGF-β1）、成纤维细胞生长因子2（FGF2）、血小板源性生长因子（PDGF）、内皮素1（ET-1）和血管内皮生长因子（VEGF）的水平。结果光学显微镜下可见正常皮肤微血管数目较少；增生性瘢痕微血管数目增多，血管狭长扭曲甚至闭塞。透射电镜可见增生性瘢痕中毛细血管管腔狭窄，有内皮细胞脱落。增生性瘢痕中血管内皮细胞分泌TGF-β1、PDGF、ET-1、VEGF、FGF2的水平分别为（60±8）、（30±4）、（0．12±0．03）、（52±5）、（18．1±1．2）μg／个细胞，明显低于正常皮肤（P〈0．05）。结论 增生性瘢痕中血管内皮细胞生物学功能减退，可能与瘢痕中胶原的大量产生和缺氧有关。