血清胎球蛋白A和心血管钙化

心血管系统的钙化主要包括动脉钙化及瓣膜钙化。目前,其钙化发生的确切机制尚不明确。血清胎球蛋白A（Fetuin A）主要由肝脏合成和分泌,具有多种不同的生物学作用，其在血液循环中含量丰富，是强有力的钙化抑制因子。近年来,关于胎球蛋白A对心血管系统钙化的凋节作用的研究逐渐增多。本文就有关胎球蛋白A的研究进展作一综述。     

Biology of vascular calcification in renal disease

The high rates of atherosclerotic vascular disease in patients with end-stage renal disease (ESRD) cannot be fully explained by the excess of traditional risk factors. Interest has therefore arisen in the possible role of vascular calcification, which is increased in these patients and may effect plaque stability and have detrimental hemodynamic consequences. Considerable evidence has accumulated recently pointing to the regulated nature of the calcification process. The initiation of calcium crystal formation appears to require the presence of small membrane bound vesicles released by living or apoptotic cells. The cellular release, content and phagocytosis of these vesicles appear to be important regulatory pathways in vascular calcification. Better understanding of these mechanisms may have therapeutic potential in reducing the adverse cardiovascular event rates in patients with (ESRD).     

“软脉1号”制剂对小鼠动脉钙化的预防作用

背景：原儿茶醛对引起动脉钙化的氧化应激、炎症、钙离子失衡等机制有作用,维生素E对引起动脉钙化氧化应激、免疫紊乱、炎症、血脂异常等机制也有作用,“软脉1号”制剂由原儿茶醛与维生素E两药组成.目的：用超生理剂量维生素D 3联合高脂乳剂建立小鼠动脉钙化模型,探讨“软脉1号”制剂对小鼠动脉钙化的预防作用.方法：清洁级KM小鼠40只,随机摸球法均分为正常对照组、模型组、普伐他汀钠组和“软脉1号”制剂组,后3组建立小鼠动脉钙化模型,然后分别给药干预.实验6周后眼球取血处死小鼠,制作胸主动脉苏木精-伊红染色病理切片,观察胸主动脉、血脂、红细胞和血红蛋白的变化.结果与结论：模型组可见胸主动脉有大量黑色钙质沉积于中层弹性纤维中,波浪状的弹性纤维已无法辨清,间距扩大甚至断裂,部分平滑肌细胞坏死消失,内外弹性膜结构不完整,血清总胆固醇、高密度脂蛋白升高（P 〈0.05）,血红蛋白、平均红细胞血红蛋白含量降低（P 〈0.05）.普伐他汀钠组胸主动脉血管病变无明显改善,总胆固醇、低密度脂蛋白、高密度脂蛋白、血红蛋白、平均红细胞血红蛋白、红细胞数较模型组均无显著性意义.“软脉1号”制剂组小鼠胸主动脉血管病变明显减轻,黑色钙质在弹性纤维中沉积较少,内弹性膜与中层弹性纤维均呈粉染、清晰,弹性纤维间距减少,可见呈波浪状的弹性纤维,内外弹性膜的结构比较完整.与模型组比较,“软脉1号”制剂组总胆固醇下降（P 〈0.05）,血红蛋白、平均红细胞血红蛋白含量升高（P 〈0.05）,其他指标均无统计学意义.说明“软脉1号”制剂对超生理剂量维生素D 3联合高脂乳剂造成的小鼠血管钙化具有预防作用.     

The progression and impact of vascular calcification in peritoneal dialysis patients.

BACKGROUND: Progression of coronary artery calcification (CAC) has been described in hemodialysis patients, and severe CAC has been associated with the occurrence of cardiovascular events in this population. Little information is available regarding peritoneal patients. AIM: To prospectively evaluate peritoneal dialysis patients in order to identify the variables associated with the rate of CAC progression, as well as to determine the impact that baseline CAC has on clinical outcomes over a 1-year follow-up period. METHODS: Using multislice coronary tomography, calcium scores were estimated at baseline and after 12 months in 49 peritoneal dialysis patients. Patients with and without CAC progression were compared with respect to clinical characteristics and biochemical variables, including lipid profile, parameters of mineral metabolism, and markers of inflammation. Cardiovascular events, hospitalizations, and all-cause mortality were recorded. RESULTS: At baseline, 29 patients (59%) presented CAC and a median calcium score of 234.7 (range 10.3-2351) Agatston units. Progression of CAC was observed in 13 patients (43%) who, in comparison with those presenting no CAC progression, were older, presented higher baseline calcium scores, and had higher mean glucose levels, lower mean high density lipoprotein cholesterol levels, and more months using low calcium peritoneal solution. We also observed a trend toward more often presenting with a history of hypertension, exhibiting more hyperphosphatemic and hyperglycemic events, and having lower albumin levels. In multiple logistic regression, only baseline calcium score was independently associated with progression of CAC. A shorter cardiovascular event-free time and a trend toward lower survival rates were observed in the group with CAC. Hospitalization event-free time did not differ between the groups. CONCLUSION: Determining CAC provides important prognostic data in peritoneal dialysis patients. Baseline calcium score and disturbances in glucose, mineral, and lipid metabolism were indicative of higher risk of CAC progression in this population.     

血管钙化的影响因素及预测指标

目的 分析血管钙化的预测因素,探究血管钙化的有效预测指标.方法 回顾性分析河北医科大学第一医院血管外科2018年8月至2020年7月收治的患者467例,依据有无血管钙化分为病例组及对照组,并收集其临床资料.通过单因素及多因素Logistic回归分析血管钙化的影响因素,绘制受试者工作特征(receiver operati...     

内皮细胞在血管钙化进程中的作用

血管钙化为糖尿病、高血压、终末期肾病等所致血管病变的共同病理基础,是心血管事件发生的独立危险因素。目前普遍认为血管钙化是与骨矿化类似的、受细胞与基因主动调控的生物过程,因而阐明参与血管钙化的发病机制具有显著的临床意义。最近研究发现,在病理状态下内皮细胞可通过调节自身状态及周围微环境参与血管钙化的发生,明确钙化细胞来源与作用可为血管钙化防治提供新的途径。     

Effects of adrenomedullin on vascular calcification in rats

Summary Objective The aim of the present study was to investigate the effect of adrenomedullin (ADM) on vascular calcification. Methods The vascular calcification model was established in rats (VND group) by using vitamin D₃ (300000IU/kg) and nicotine (25mg/kg, two doses). The effect of liposome-encapsulated ADM was observed. Vascular calcium content, alkaline phosphatase (ALP) activity, ADM in aortic tissue and plasma, binding ability of ¹²⁵I-ADM for ADM receptor on vascular plasma membrane and content of cAMP in vessels were measured. Results Compared with control rats, the aortic calcium content and vascular ALP activity in rats of the VDN group was obviously increased; in addition ADM concentrations in plasma and vessels of rats in VDN group were increased. But the maximum binding sites of ¹²⁵I-ADM for ADM receptor (Bmax) on vascular plasma membrane in rats of VDN group were significantly decreased compared with control rats. The affinity of ¹²⁵I-ADM for the ADM receptor was reduced, as shown by the Kd value and vascular cAMP content being reduced in rats of the VDN group compared to the control group. The in vitro response of isolated vessels to ADM incubation was weakened. Administration of empty liposome had no effect on vascular calcification. But administration of ADM significantly decreased vascular calcium content and ALP activity. The Bmax of ¹²⁵I-ADM for ADM receptors on vascular plasma membrane increased by 17.7% (p<0.01), and the value of Kd decreased by 36.2% (P<0.01) in rats treated with ADM as compared with rats of the VDN group. In addition, the vascular cAMP content and the response to ADM in isolated aorta were markedly increased. Conclusion Vascular calcification induced an alteration of the vascular ADM-ADM receptor-cAMP pathway. Treatment with exogenous ADM inhibited vascular calcification by improving the vascular ADM-ADM receptor-cAMP pathway. Received: 24 September 2001 Accepted: 29 January 2002     

Cutaneous gangrene, vascular calcification, and hyperparathyroidism

We describe the development of necrotic ulcers with underlying vascular calcification in a 72-year-old man who had chronic renal failure. These lesions had surrounding ecchymoses. The patient had a normal serum calcium concentration, an elevated parathyroid hormone level, and findings consistent with a parathyroid adenoma on ultrasonography. We consider this another case of a characteristic cutaneous syndrome secondary to underlying vascular calcification and hyperparathyroidism.     

血管钙化治疗新进展

血管钙化常见于慢性进展性肾病患者且预后不理想。其发病机制复杂,极易引发多种疾病,包括心血管疾病、炎症、氧化应激、尿毒症等,严重影响着肾脏在内的各脏器功能。病理生理学研究证实了血管钙化是一个涉及矿物代谢的多因素的过程,全身和局部因素的改变可以促进或抑制血管钙化,这些都是潜在的治疗目标。但当前的治疗与预防动脉钙化仍然缺乏有效的治疗手段。     

维生素K依赖蛋白抑制血管钙化研究进展

血管钙化曾被认为是机体钙磷代谢失衡所致的钙磷复合物在血管壁被动沉积病理过程。近年血管钙化分子机制研究结果表明,血管钙化的形成类似于骨发育过程,具有主动的、高度可调控的生物学特性。维生素K依赖蛋白——基质Gla蛋白(MGP)、生长抑制特异蛋白6(Gas6)和Gla富含蛋白(GRP)参与血管钙化的调节过程,MGP已被证实是抑制血管钙化的重要蛋白,Gas6可通过抑制血管平滑肌细胞凋亡,从而抑制血管钙化。     

慢性肾脏病血管钙化的发生机制

<正>心血管疾病(cardiovascular diseases,CVD)是终末期肾病(end stage renal diseases,ESRD)患者的主要并发症之一,血管、心脏瓣膜和心肌的钙化是导致患者发生CVD的重要原因,ESRD患者中80%的动脉病变和90%的冠心病都与血管钙化     

Sortilin mediates vascular calcification via its recruitment into extracellular vesicles

Vascular calcification is a common feature of major cardiovascular diseases. Extracellular vesicles participate in the formation of microcalcifications that are implicated in atherosclerotic plaque rupture; however, the mechanisms that regulate formation of calcifying extracellular vesicles remain obscure. Here, we have demonstrated that sortilin is a key regulator of smooth muscle cell (SMC) calcification via its recruitment to extracellular vesicles. Sortilin localized to calcifying vessels in human and mouse atheromata and participated in formation of microcalcifications in SMC culture. Sortilin regulated the loading of the calcification protein tissue nonspecific alkaline phosphatase (TNAP) into extracellular vesicles, thereby conferring its calcification potential. Furthermore, SMC calcification required Rab11-dependent trafficking and FAM20C/casein kinase 2–dependent C-terminal phosphorylation of sortilin. In a murine model, Sort1-deficiency reduced arterial calcification but did not affect bone mineralization. Additionally, transfer of sortilin-deficient BM cells to irradiated atherosclerotic mice did not affect vascular calcification, indicating a primary role of SMC-derived sortilin. Together, the results of this study identify sortilin phosphorylation as a potential therapeutic target for ectopic calcification/microcalcification and may clarify the mechanism that underlies the genetic association between the SORT1 gene locus and coronary artery calcification.     

血液透析患者血浆胎球蛋白A水平及其与血管钙化的关系

目的观察血液透析患者血管钙化的发生情况,探讨血浆胎球蛋白A水平与血管钙化的关系。方法收集北京大学人民医院入选血液透析患者的人口学及临床资料,用X线平片对腹部、骨盆、手部进行血管钙化的定量测量,并检测血胎球蛋白A及C反应蛋白、全段甲状旁腺激素（iPTH）等与血管钙化相关的指标,进行相关分析。结果入选50例血液透析患者,X线平片显示66．0％（33例）有不同程度、不同部位的血管钙化。存在血管钙化的患者中90．9％有腹主动脉钙化,36．4％存在中小动脉（包括髂动脉、股动脉、桡动脉、手指动脉）钙化,有中小动脉钙化的患者中75．0％存在腹主动脉钙化。另外中重度血管钙化者占33．3％。中、重度血管钙化与轻度血管钙化患者比较,年龄更大,男性比例高,糖尿病比例高,舒张压低（P〈0．05）。血液透析患者血浆胎球蛋白A水平较健康对照组明显降低（P 〈0．01）,中、重度血管钙化的血液透析患者血浆胎球蛋白A水平明显低于无／轻度钙化患者（P〈0．01）。多元线性回归分析显示血管钙化积分、血白蛋白水平是血胎球蛋白A浓度的独立影响因素。结论血液透析患者普遍存在血管钙化,以腹主动脉钙化为突出表现,血管钙化积分、白蛋白水平是血胎球蛋白A浓度的独立影响因素。     

尿毒症患者血管钙化相关因素的分析

目的 探讨尿毒症患者血管钙化发生的相关因素.方法 85例尿毒症患者,均行颈总动脉B超检查及胎球蛋白A、血磷、血钙、C-反应蛋白等检测.结果 有血管钙化的尿毒症患者胎球蛋白A水平明显低于无钙化者[(2.34±0.95)μg/L与(3.79±1.19)μg/L,t=5.94,P＜0.01],而血磷、钙磷乘积及C-反应蛋白水平高于非钙化组[血磷:(1.97±0.23)mmol/L与(1.80±0.33)mmol/L,t=2.05,P＜0.05;钙磷乘积:(50.04±6.61)mg~2/dl~2与(44.84±9.75)mg~2/dl~2,t=2.05,P＜0.05;C-反应蛋白:(33.45±25.11)mmol/L与(20.65±13.43)mmol/L,t=2.03,P＜0.05].相关性分析显示胎球蛋白A水平与C-反应蛋白(r=-0.43,P＜0.01)、血钙磷乘积(r=-0.32,P＜0.01)、血白蛋白(r=0.37,P＜0.05)及血磷(r=-0.36,P＜0.05)相关.结论 高血磷、钙磷乘积升高和微炎症状态是尿毒症患者血管钙化的危险因素,血胎球蛋白A水平降低导致尿毒症患者血管钙化,补充外源性胎球蛋白A可能成为一种预防血管钙化的有效手段.     

血液透析患者血管钙化的防治

心血管疾病是慢性肾脏病（CKD）患者的第一死亡原因，占50％左右。钙磷代谢紊乱导致的血管钙化在其中具有重要作用。当钙和（或）磷浓度在局部和循环中的浓度超过磷酸盐的溶解度乘积时，不溶解的碱性磷酸钙（BCP）在细胞外基质沉积，导致血管钙化。CKD5期患者冠状动脉和血管钙化的发生率高于一般人群，且随年龄和透析时间增加而增高，年轻透析患者比正常人早几十年发生血管钙化。透析20年和50岁以上透析患者，100％有血管钙化。用电子束CT（EBCT）检查，20～30岁透析患者16例中14例有血管钙化，而同龄正常人60例中仅有3例。