Longitudinally orientated smooth muscle cells in rabbit arteries

Intima formation in vessels, spontaneous or experimentally induced, is generally characterized by the presence of longitudinally orientated smooth muscle cells (LSMC). During an experiment of neo-intima induction in carotid arteries in rabbits, by application of a nonconstrictive silastic cuff, a study was performed to investigate the presence of LSMC in the systemic and pulmonary circulations, in both elastic and muscular arteries. Three patterns could be distinguished: intimai cushions in muscular arteries, single or small groups of LSMC in the intima in elastic and larger muscular arteries, and intra-medially located layers or columns of LSMC in the aorta, the pulmonary artery, at the bifurcation of the aorta and around orifices of branches. In order to understand this peculiar orientation a biomechanical approach was used: this showed that near the lumen the circumferential stress is 4.5 times higher than the longitudinal. Because the cell surface of the smooth muscle cells exposed to this stress per unit vessel length is much less in the longitudinal than in the circular direction we conclude that the LSMC align in the direction which allows them to cope most effectively with the mechanical stresses.     

Expression of cell cycle regulators during smooth muscle cell proliferation after balloon catheter injury of rat artery

Intimal hyperplasia is defined as the abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) with deposition of extracellular matrix. However, the cell cycle regulatory mechanisms of injury-induced VSMC proliferation are largely unknown. To examine the expression kinetics of cell cycle regulatory factors which is known to be worked positively or negatively, we used rat balloon injury model. Marked induction of proliferating cell nuclear antigen (PCNA), G1/S cyclin-dependent kinase (cdk2), and its regulatory subunit (cyclin E) occurred between 1 and 3 days after balloon arterial injury, and this was sustained for up to 7 days and then declined. However, the induction of the negative regulators, p21 and p27, occurred between 3 and 5 days of injury, peaked after 7 and 14 days and was then sustained. VSMC proliferation after balloon catheter injury of the rat iliac artery is associated with coordinated expression of positive (cdk2, cyclin E and PCNA) and negative (p21, p27) regulators. Cell cycle regulators such as cdk2, cyclin E, p21, p27 may be suitable targets for the control of intimal hyperplasia.     

COX基因多态性与缺血性卒中的相关性研究

【摘要】 目的 探讨环氧合酶(COX)代谢通路基因多态性及其与缺血性卒中发病率的关系。方法 将2013年2月~2015年11月在德阳市人民医院和温州医科大学第三附属医院神经内科住院经头颅CT和MRI检查确诊的299例急性缺血性卒中患者,根据彩超结果分为颈动脉易损斑块组（VP）94例、稳定斑块组（SP）74例和无斑块组（NP）131例;同时再分为颈动脉内膜增厚组（IT）108例和非内膜增厚组（NT）191例。使用聚合酶链反应和质谱分析测定基因多态性,包括前列腺素合酶1(PTGS1 rs1236913)、前列腺素H合酶2(PTGS2 rs689466)、血栓素A2合酶(TBXAS1 rs2267679、rs41708、rs194149)、前列腺素E合酶(PTGES2 rs6478818)、环前列腺素合成酶(PTGIS rs5602、rs5629)。结果 在易损斑块组和无斑块组之间TBXAS1 rs194149 GG基因型(P=00281),PTGIS rs5602 CT基因型(P=00319)存在显著差异。内膜增厚组和非内膜增厚组之间PTGS2 rs689466 GG基因型(P=00216)显示显著差异。多元回归分析显示,PTGIS的AA基因型(P=00308,OR:0275,95%CI:0079～0955)和PTGS2的AG+ GG基因型(P=00065,OR:2162,95%CI:1232～3795)是内膜增厚的破坏性因素。结论 COX的单核苷酸多态性(SNP)与脑梗死的发病率存在相关性,PTGIS和PTGS2基因多态性与内膜增厚脑卒中患者相关。     

2型糖尿病肾功能损害与颈动脉内-中膜厚度的关系研究

目的探讨2型糖尿病(T2DM)患者颈动脉内-中膜厚度(IMT)与肾功能损害的关系。方法选取60例健康体检者(对照组)、60例单纯糖尿病者(A组)、60例糖尿病肾病肾功能正常者(B组)和60例糖尿病肾病肾功能不全者(C组),检测并比较4组受检者的血压、血糖、血脂、C肽、尿微量清蛋白等水平及颈动脉IMT,分析与颈动脉IMT相关的指标。结果对照组、A组、B组和C组受检者的颈动脉IMT分别为(0.63±0.11)、(0.89±0.20)、(1.03±0.23)、(1.37±0.26)mm,4组间比较差异有统计学意义(F=132.190,P<0.01)。且B、C组受检者的颈动脉IMT显著高于对照组及A组,且C组又显著高于B组,差异有统计学意义(P<0.01)。多元逐步回归分析显示,T2DM患者的颈动脉IMT与尿清蛋白排泄率呈正相关(P<0.01)。结论 T2DM患者颈动脉IMT与肾功能损害密切相关,早期应用颈部B超测定颈动脉IMT对诊断T2DM肾损害具有重要意义。     

颈动脉内膜中膜厚度联合踝臂指数对冠心病预测价值的研究

目的研究颈动脉内膜中膜厚度（IMT）联合踝臂指数（ABI）对冠心病的预测价值。方法选择2008至2010年在日照市人民医院住院并行冠状动脉造影或介入治疗患者194例,术前对其进行颈动脉内膜中膜厚度以及踝臂指数测量,血液生化检查,病史采集,并根据ABI≤0．90为阳性,ABI〉0．90为阴性,IMTI〉0．9mm为阳性,IMT〈0．9mm为阴性,设定为两项指标均为阴性为A组,ABI阳性为B1组,阴性为B2组,IMT阳性为C1组,阴性为C2组,两项指标均为阳性者为D组,并根据冠状动脉造影结果得出各组冠心病发病率。结果A组中冠心病发病率为9．1％,B1组为64．8％,B2组为29．9％,C1组为70．8％,C2组为28．4％,D组为89．1％,从以上结果中我们可以看出,踝臂指数阳性能较好预测冠心病发生（B1：64．8％比B2：29．9％,P〈0．05）;颈动脉内膜中膜厚度对冠心病的预测也有重要意义（C1：70．8％比C2：28．4％,P〈0．05）,两项指标均为阳性对冠心病的预测价值要高于单一项指标（D：89．1％比B1：64．8％,C1：70．8％,P〈0．05）,且两项指标阴性对冠心病的排除价值也要高于单一项指标阴性者（A：9．1％比B2：29．9％,C2：28．4％,P〈0．01）。结论联合应用ABI、IMT两项指标对冠心病的预测具有重要的临床意义。     

Mean HbA1c over 18 years predicts carotid intima media thickness in women with type 1 diabetes

Aims/hypothesis Intima media thickness (IMT) of the common carotid artery (CCA) is a validated surrogate marker of early atherosclerosis. The aim of our study was to assess the association between IMT in CCA and long-term mean HbA₁c in type 1 diabetes. We also elucidated the association between carotid IMT and preclinical coronary atherosclerosis.Methods In 39 individuals with type 1 diabetes, HbA₁c was measured prospectively over 18 years. The IMT examinations were performed with high-resolution ultrasound. The association between carotid IMT and preclinical coronary atherosclerosis (assessed by intravascular ultrasound [IVUS]) was tested in 29 of the patients.Results Mean HbA₁c over 18 years was 8.2% (range: 6.6–11.3%). Mean age at follow-up after 18 years was 43 years and mean duration of diabetes was 30 years. IMT was significantly higher in diabetic patients than in an age- and sex-matched reference population. The IMT values were at the same level as for controls who were 20 years older. In women, HbA₁c was significantly associated with mean average CCA IMT (r²=0.77, p<0.0001 when adjusted for age), whereas there was no significant association for men. Among women, a significant association was also found between carotid IMT and the percentage of coronary vessel area stenosis (r=0.65, p=0.03).Conclusions/interpretation The present findings suggest an important role of long-term hyperglycaemia in the development of atherosclerosis, especially in women with type 1 diabetes.Type 1 diabetes patients have earlier development of, and more advanced, atherosclerosis compared with an age- and sex-matched reference population. In women, carotid IMT reflects preclinical coronary atherosclerosis.     

Influence of the Mediterranean diet on carotid intima–media thickness in hypercholesterolaemic children: A 12-month intervention study

Background and aimsThe Mediterranean diet has been recognised as having a protective role on the cardiovascular system due to its low lipid and high antioxidant content. Lipid profile and oxidant status represent two important risk factors related to endothelial dysfunction, even at early stages of cardiovascular diseases. The aim of the study was to evaluate the influence of a 12-month Mediterranean diet on the variation of lipid profile and carotid intima–media thickness (cIMT) in pre-pubertal hypercholesterolaemic children.Methods and resultsWe performed a cross-sectional study comparing lipid profile and cIMT in a group of 68 pre-pubertal children (36 with hypercholesterolaemia and 32 controls). In addition, in the hypercholesterolaemic children a 12-month intervention programme with a Mediterranean diet was started to evaluate the variation of lipid profile and cIMT. At baseline, hypercholesterolaemic children showed a significantly higher cIMT (both right and left carotid artery) compared to controls (both p < 0.05). After 12 months of diet intervention, a significant reduction of total cholesterol, LDL-cholesterol and cIMT was documented (all p < 0.05). Furthermore, at the end of follow-up, delta body mass index-Standard Deviation score and delta LDL-cholesterol were significantly and independently related to the changes of cIMT (both p < 0.05).ConclusionThe Mediterranean diet represents a valid approach in the treatment of hypercholesterolaemia even during childhood.     

全反式维甲酸对兔颈动脉粥样硬化病变中Cdk2表达及血管平滑肌细胞增生的影响

目的探讨全反式维甲酸(ATRA)对兔颈动脉粥样硬化病灶中血管内膜的增生、血管平滑肌细胞(VSMCs)增殖、增殖细胞核抗原(PCNA)及细胞周期素依赖性激酶Cdk2表达规律的影响。方法36只新西兰雄性大白兔随机分为3组:正常饮食组、手术组、ARTA治疗组,每组12只。手术组和治疗组均给予高脂饮食,两周后用空气干燥法制作颈动脉内膜损伤模型,治疗组于术前3d开始给予ATRA灌胃。于术后1、4周处死动物,取病变血管应用HE染色、免疫组化和计算机图像分析法进行形态学、PCNA和Cdk2表达水平的检测。结果①正常动脉壁未见PCNA及Cdk2表达。②手术组在术后第1周时内膜开始增生,第4周增生明显,且出现泡沫细胞、脂质核心形成、管腔狭窄;增生内膜中Cdk2表达水平增高。③治疗组Cdk2的表达明显低于手术组(P<0.05),VSMCs的迁移、增殖、内膜增生和管腔狭窄显著减轻(P<0.05)。④PCNA表达与Cdk2表达呈显著正相关(P<0.01)。结论ARTA可通过抑制Cdk2表达,抑制VSMCs的迁移和增殖,从而抑制兔颈动脉粥样硬化新生内膜过度增生和管腔狭窄。     

去除外膜对血管内膜增殖及反应性的影响

目的:观察去血管外膜后兔颈动脉血管内膜增殖及血管反应性改变的情况。方法:在体去除兔颈动脉外膜,于术后0周及1周时取出动脉作组织学检查,血管张力测试,免疫组织化学染色,用RT-PCR法测定返原型辅酶Ⅱ氧化酶P22亚单位(NADPH Oxidase P22Phox)信使核糖核酸(mRNA)。结果:(1)外膜去除方法对血管内皮及中层平滑肌无明显损伤;(2)外膜去除后血管内膜增生,增生成分为血管平滑肌细胞;(3)与完整外膜血管比较,去外膜血管对去甲肾上腺素(NE)的收缩反应在术后即刻及1周均减弱(P<0.05),对乙酰胆碱(Ach)的舒张反应在术后即刻增强(P<0.05);(4)与完整外膜血管比较,去外膜血管NADPH Oxidase P22Phox在1周时表达增高(P<0.05)。结论:外膜去除可致兔颈动脉内膜增生,同时引起血管舒缩反应性发生改变。