Association analysis of genes in the renin‐angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: The Diabetes Heart Study

Aims Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin‐angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). Methods Atherosclerosis was measured by carotid intima‐media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. Results Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. Conclusions Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population.     

Homocysteinylation of low-density lipoproteins (LDL) from subjects with Type 1 diabetes: effect on oxidative damage of human endothelial cells.

BACKGROUND: Homocysteine (Hcy) is an independent risk factor for cardiovascular disease (CVD). Individuals with Type 1 and Type 2 diabetes are more susceptible to the effects of homocysteine than non-diabetic subjects. The interaction between homocysteine-thiolactone (Hcy-thiolactone), a reactive product of Hcy, and low-density lipoproteins (LDL) induces the formation of homocystamide-LDL adducts (Hcy-LDL) and it has been suggested that homocysteinylation could increase atherogenicity of lipoproteins. AIM: The aim of the study was to compare the effect of in vitro homocysteinylation of LDL isolated from healthy control subjects (C-LDL) and from Type 1 diabetic patients (DM-LDL) and to investigate the effect of homocysteinylated LDL (Hcy-C-LDL and Hcy-DM-LDL) on peroxynitrite production of endothelial cells. METHODS: The in vitro homocysteinylation of LDL isolated from control (n = 12) and DM subjects (n = 12) was carried out by incubating lipoproteins with Hcy-thiolactone. The reaction was verified by quantifying the increase in sulphydryl groups (-SH groups) in Hcy-LDL with respect to control LDL. Control and homocysteinylated LDL were incubated with human aortic endothelial cells (HAEC) in culture. Peroxynitrite production in cells treated in different experimental conditions was assayed by a fluorimetric method. RESULTS: The increase in -SH groups after incubation with homocysteine was greater in LDL from diabetic subjects compared with LDL from control subjects (P < 0.001). In addition, peroxynitrite production from HAEC incubated with Hcy-LDL from diabetic patients was greater than after incubation with Hcy-LDL from control subjects and untreated LDL from diabetic patients (P < 0.001). CONCLUSIONS: These results show that LDL from diabetic patients is more susceptible to in vitro homocysteinylation than LDL from non-diabetic individuals and demonstrate that the compositional changes in Hcy-LDL from diabetic subjects have cytotoxic effects on human endothelial cells.     

颈动脉粥样硬化斑块内MCP-1表达的研究

目的观察颈动脉粥样硬化(AS)斑块内单核细胞趋化蛋白-1(MCP-1)的mRNA和抗原的表达情况。方法分别应用原位杂交和免疫组织化学法测定颈AS斑块中MCP-1mRNA和抗原表达。结果相对于正常动脉内膜,颈AS病变内膜MCP-1阳性细胞数明显增多(P<0.05)。其中颈AS严重病变肩区阳性细胞数最多,以单核-巨噬细胞为主。结论MCP-1与颈AS发生密切相关。     

支架术治疗颈动脉狭窄的临床研究

目的　观察支架术治疗颈动脉狭窄的近期疗效 ,探讨临床应用中的相关问题。方法　将临床经颈部B超、脑血管造影确诊的颈动脉狭窄患者 10 8例 ,实施颈动脉支架术 ,15例行预扩张 ,12例后扩张成形 ,9例使用滤器装置 ,围手术期给予抗血小板聚集等治疗。结果　 2例手术失败 ;术后 2例发生脑出血 ,1例脑栓塞 ,1例支架内血栓形成 ,除 1例脑出血死亡外 ,3例治疗后恢复 ;1～ 6个月的随访中 ,10 5例患者无复发。手术并发症发生率低 ,近期疗效满意。结论　颈动脉狭窄段支架术治疗颈动脉狭窄具有可行性 ,近期疗效肯定 ,是临床上有推广潜力的治疗颈动脉狭窄的方法 ,但远期疗效尚需进一步观察。     

Measurement of nonlinear property of artery wall using remote cyclic actuation

Purpose For tissue characterization of the arterial wall, we developed a “phased tracking” method to measure the strain (change in wall thickness) and elasticity of the arterial wall. To improve the accuracy of tissue characterization, we are now attempting to measure other mechanical properties in addition to elasticity. Methods In this study, the change in elasticity during the cardiac diastole was measured with ultrasound by generating a change in internal pressure using remote cyclic actuation. Results From the measured change in elasticity during cardiac diastole, the nonlinear property in the stress–strain relationship of the artery wall was estimated. In basic experiments using a silicone rubber tube and in vivo experiments in human carotid arteries. Conclusion The proposal method enables the noninvasive measurement of the nonlinear mechanical property in addition to the elasticity of the arterial wall.     

Apopotic gene Bax expression in carotid plaque

The expression of BAX in carotid atherosclcrosis and its regulation is far from defined. Objectives To investigate BAX expression in stable/fibrous and instable/vulnerable carotid plaque and its clinical significance. Methods 25 cases of carotid plaque specimens obtained from endarterectomy were divided into two groups, stable/fibrous 14 cases, vulnerable/instable 11 cases; aortic artery and its branches from hepatic transplantation donors 6 case as control. The expression of proapoptotic BAX was detected by immunohistochemistry (IHC), in situ hybridization(ISH) and in situ TdT dUTP nick end labeling (TUNEL). Results 5 eases of BAX ( ) were detected by ICH and ISH, 4 case of TUNEL ( ) were detected by TUNEL in stable/fibrous carotid plaque, while 10 cases were BAX ( )by IHC(P<0.05) , 11 case by ISH and 9 case by TUNEL were detected in instable/vulnerable carotid plaque (P<0.01), respectively. The intensity of BAX ( ) cells by IHC and ISH was 8.63±2.62 and 10.32±3.12 in fibrous plaques, whereas 122±21.64 and 152±23.35 in vulnerable plaques, respectively. No expression of BAX was found in controlled group. Conclusion The higher expression of Bax in vulnerable carotid plaque may be one mechanisms in molecular pathogenesis of carotid atherosclerosis which affect plaque stability and be the cause of higher incidence of stroke than fibrous carotid plaques, the regulation of BAX expression in different stage of atherosclerosis may provide targets in gene therapy for carotid atherosclerosis.     

糖耐量减低患者胰岛素抵抗与颈动脉粥样斑块的相关性分析

目的　探讨胰岛素抵抗 (IR)在糖耐量减低 (IGT)大血管并发症中的作用。方法　测定 1 2 0名IGT患者和 96名糖耐量正常(NGT)对照者的空腹血糖 (FBG)、胆固醇 (TC)、甘油三酯 (TG)、胰岛素 (FINS)及餐后 2h血糖 (PBG) ,并测量身高、体重、腰围、臀围 ,计算相对胰岛素敏感指数 (RISI)、体重指数 (BMI)、腰臀比 (WHR) ,结合其颈动脉多普勒超声检测结果进行对比分析。结果　IGT组及NGT组颈动脉粥样斑块发生率有显著性差异 (P <0 .0 0 1 ) ,斑块面积与RISI呈负相关 (r =- 0 .45 ,P <0 .0 1 ) ,与餐后 2h血糖 (r =0 .39,P <0 .0 1 )、BMI(r=0 .48,P <0 .0 1 )及WHR(r=0 .41 ,P <0 .0 1 )正相关 ,而与TG、FBG、TC、FINS无相关性 (P >0 .0 5)。IGT组患者有斑块和无斑块者之间RISI、WHR、BMI、餐后 2h血糖、TG之间也存在显著性差异 (P <0 .0 1 )。结论　胰岛素抵抗与颈动脉粥样硬化的发生密切相关 ,是IGT患者发生大血管并发症的重要原因。     

腔内超声对颈动脉支架成形术的评估

目的评估血管腔内超声(IVUS)在颈动脉狭窄血管内支架成形术中的应用价值。方法应用IVUS对18例颈动脉狭窄患者进行颈动脉内壁病变判断,指导支架置入并观察血管内支架置入前后血管形态学改变。并以8个正常患者的颈动脉管壁IVUS图像作为对照组。结果IVUS清晰显示血管壁的形态结构,精确测量血管狭窄程度。本组18例均接受血管内支架成形手术,成功置入支架18枚;经6-52个月随访(平均28个月),除2例于术后30d内TIA发作外,无一例脑梗死和再狭窄发生。结论IVUS比DSA更精确判断颈动脉病变性质、狭窄程度以及血管内支架术后的管腔变化,指导选择合适的球囊扩张管腔。IVUS引导支架置入可能有效预防再狭窄的发生。     

小檗碱对兔颈动脉粥样硬化中内膜增生和巨噬细胞趋化作用的影响

目的观察小檗碱对家兔颈动脉粥样硬化的内膜中膜比和巨噬细胞变化的影响。方法24只雄性日本大耳白兔随机分为3个试验组,正常组每天肌肉注射生理盐水,普通饲料喂养,对照组高脂喂养,1周后行颈动脉内膜空气干燥术并每日肌肉注射生理盐水,小檗碱干预组高脂喂养,1周后行颈动脉内膜空气干燥术并肌肉注射小檗碱,5周时取手术侧的颈动脉做弹力纤维染色,计算内膜中膜比;巨噬细胞免疫组化检测巨噬细胞在颈动脉粥样硬化病变中的变化,计算巨噬细胞的阳性率。结果对照组内膜厚度明显增加,中膜萎缩变薄,经计算I/M为1.20±0.007,小檗碱组的I/M为0.65±0.008。两组间有显著差异(P<0.01);巨噬细胞免疫组化染色对照组内膜下和中膜有大量巨噬细胞,小檗碱干预组内膜和中膜下也可以见有巨噬细胞沉积,通过计算巨噬细胞阳性率,小檗碱干预组的巨噬细胞阳性率明显小于对照组(P<0.01)。结论小檗碱可以降低家兔颈动脉粥样硬化中的血管内膜厚度、减少粥样斑块中的巨噬细胞数目,从而干预颈动脉粥样硬化的形成。     

Localized pleural plaques and lung cancer.

In a mass chest radiography survey conducted in 1971 for 7,986 residents of three Finnish communities, 604 subjects (7.6%) with pleural plaques but not other asbestos-related radiographic signs were identified. The same number of referents, each individually matched to each plaque carrier on sex, birth year, and community, was selected from among persons in the same source population with no pleural plaques. The two groups were followed for investigation of incidence of lung cancer during 1972-1989. Twenty-eight of those with plaques and 25 referents contracted lung cancer (crude conditional RR = 1.1; CL95 = 0.7, 1.9). The application of the proportional hazards model, with adjustment for sex, age, and residence, resulted in a hazard ratio of 1.1 (CL = 0.6, 1.8). The risk ratio estimate may be biased; hence, the result is inconclusive in regard to the predictive assessment of lung cancer risk among carriers of pleural plaques.