一个新的心血管疾病标志物——心锚重复蛋白

心锚重复蛋白属于锚蛋白重复序列蛋白家族成员,是一个核转录辅助因子,在转录过程中起辅助激活物和辅助阻遏物的作用。心锚重复蛋白受Nkx2.5、转化生长因子-β/Sm ad、p38丝裂原激活的蛋白激酶等多条信号通路调节,在心脏生长发育、血管新生、细胞凋亡、维持心肌结构和功能的完整性、心肌肥厚、动脉粥样硬化和心律失常等多方面发挥作用。     

心房颤动患者血清心锚重复蛋白的变化及临床意义

目的:探讨血清心锚重复蛋白(CARP)在心房颤动(房颤)中的变化及临床意义。方法:选择房颤组64例和窦性心律(窦律)组60例,采用酶联免疫吸附法(ELISA法)检测入选者血清CARP浓度,并对结果进行统计学分析。结果:房颤组CARP水平高于窦律组[(8.08±1.23)ng/L∶(7.09±1.05)ng/L,P<0.05],持续性房颤亚组CARP水平高于阵发性亚组[(8.24±1.27)ng/L∶(7.83±1.30)ng/L,P<0.05]。结论:房颤患者的血清CARP浓度水平明显增高,血清CARP浓度水平与心房颤动的发生和维持有一定联系。     

心锚重复蛋白、肌红蛋白、α1-微球蛋白在急性心肌梗死中的临床意义

目的 探讨血清心锚重复蛋白（CARP）、肌红蛋白（Myo）、α1-微球蛋白在急性心肌梗死患者中的表达及意义。方法 选取2019年2月至2019年8月在东南大学附属中大医院接受治疗的急性心肌梗死型患者65例为急性心肌梗死组,另选取同期于我院接受常规体检的健康志愿者65例为对照组。使用酶联免疫吸附法检测CARP,化学发光免疫法检测Myo水平,免疫透射比浊法检测α1-微球蛋白、心肌肌钙蛋白I(cTnI)、超敏肌钙蛋白（hs-TNI）水平。结果 与对照组比较,急性心肌梗死组患者血清CARP、Myo、α1-微球蛋白、cTnI、hs-TNI水平较高,差异有统计学意义（t=7.803、29.890、29.920、26.880、18.810,P <0.05）。在急性心肌梗死患者中CARP与Myo、α1-微球蛋白及Myo与α1-微球蛋白均呈正相关（r=0.399、0.446、0.463,均P <0.01）。CARP、Myo、α1-微球蛋白与cTnI、hs-TNI水平均呈正相关（r=0.360、0.384、0.419、0.362、0.380、0.375,均P <0.01）。结论 CARP...     

冠状动脉粥样硬化病变与冠状动脉重构

目的 :本文旨在通过血管内超声进一步探讨冠状动脉 (冠脉 )粥样硬化斑块与冠脉重构间的关系。　　方法 :90例住院病人 ,男 60例 ,女 3 0例 ,年龄 3 6～ 76(5 9± 11)岁。临床诊断冠心病或可疑冠心病。均详细询问病史 ,行心电图、超声心动图、冠脉造影及血管内超声检查。　　结果 :①冠脉狭窄与血管重构的关系 :轻 (<5 0 % )、中 (5 0 %～ 75 % )、重 (>75 % )度狭窄均可见血管重构 ,以中、重度狭窄血管重构较明显。但均无明显差异 (P均 >0 0 5 )。②斑块性质与血管重构的关系 :脂质性斑块可见明显的血管重构 ,有显著性差异 (P <0 0 5 ) ,纤维性及钙性斑块血管重构不明显 (P >0 0 5 )。③斑块的形态与血管重构的关系 :61根血管为偏心性斑块 ,3 3根血管为同心性斑块 ,偏心性斑块可见明显的血管重构 ,有显著性差异 (P <0 0 5 )。同心性斑块血管重构不明显 (P >0 0 5 )。　　结论 :本文提示血管重构与斑块的性质及形态有着明显的关系 ,偏心性斑块和脂质性斑块可见明显的血管重构 ,而与血管狭窄程度无明显关系。因此 ,由于血管重构 ,血管内超声可显示明显的动脉粥样硬化斑块 ,而冠脉造影可无明显狭窄表现。     

血清淀粉样蛋白A水平与冠状动脉粥样硬化的研究进展

冠状动脉粥样硬化性心脏病，简称“冠心病”，是一种危害全球公民健康的主要疾病。所以早期识别相关生物学标志物是做到对疾病早诊断、早治疗的关键。血清淀粉样蛋白A是一种由肝脏合成的急性期蛋白，属于炎性标志物。近年来大量研究发现SAA与冠心病的发生发展存在明显的关联性。因此，本文就近年来关于SAA与冠心病的相关性的研究成果做进一步综述。     

双源CT心周脂肪定量与冠状动脉粥样硬化病变程度的相关性

目的 分析心周脂肪体积与心血管危险因素、冠心病的发生和冠状动脉狭窄程度之间的关系.方法 221例同期行64排双源CT和经皮冠状动脉造影检查的患者入选,进行腰围、体质指数和空腹血生物化学指标测定.使用64排双源CT测定心周脂肪体积,通过经皮冠状动脉造影检查明确患者的冠心病诊断和冠状动脉病变支数,并采用Gensini积分量化冠状动脉狭窄的严重程度.结果 入选患者男性占71.04%.男性心周脂肪体积明显大于女性(241.44±78.08 cm~3比216.46±64.36 cm~3,P=0.025).年龄≥70岁的患者心周脂肪体积明显大于年龄<70岁的同性别患者(P<0.05).冠心病患者的心周脂肪体积明显大于非冠心病患者(242.10±75.80 cm~3比189.23±52.26 cm~3,P<0.001).Logistic回归分析显示心周脂肪体积(OR=1.11,P<0.001)和体质指数(OR=1.01,P=0.001)是影响冠心病发生的独立危险因子.心周脂肪体积随着冠状动脉病变支数的增加而增加,并且与Gensini积分呈正相关.结论 64排双源CT可对心周脂肪组织进行准确定量,心周脂肪体积与心血管危险因素和冠心痛的发生以及冠状动脉病变程度存在较强的相关性,可作为一个新的评估冠心病风险和病变程度的指标.     

冠状动脉粥样硬化斑块消退研究进展

冠状动脉粥样硬化的发生与低密度脂蛋白及炎症反应、内皮功能减退等有关。近年来多项临床试验证实早期强化应用他汀类药物可以通过降低低密度脂蛋白、抗炎、改善内皮功能等途径改善急性冠脉综合征患者的预后。其中他汀类药物发挥的抗炎症反应、改善内皮功能等多效性作用日益受到重视。而应用血管内超声的研究发现强化他汀类治疗能够显著遏制甚至消退冠状动脉粥样斑块。     

老年人颈动脉粥样硬化与冠状动脉粥样硬化的关系

为探讨老年人颈动脉粥样硬化与冠状动脉粥样硬化的关系,对94例进行冠状动脉造影的老年患者进行颈动脉超声检查。颈动脉粥样硬化斑块积分采用Sutton法,结果发现,冠状动脉病变单支组和多支组内膜一中膜厚度,斑块积分显著高于正常组,冠状动脉病变多支组显著高于单支组（P均＜0．05）,斑块指数与年龄,吸烟,低密度脂蛋白胆固醇／高密度脂蛋白胆固醇比值,收缩压以及高血压病程及程度密切相关,结果提示,颈动脉粥样硬化与冠状动脉粥样硬化的病变是平行的。     

颈动脉粥样硬化与冠状动脉粥样硬化的关系

目的　探讨颈动脉粥样硬化与冠状动脉粥样硬化的关系。方法　对 94例老年患者进行了冠状动脉造影和颈动脉超声检查。颈动脉粥样硬化斑块积分采用Sutton法。结果　单支组及多支组内膜中膜厚度、斑块积分显著高于正常组 ,多支组显著高于单支组 (P<0 .0 5 )。斑块指数与年龄、吸烟、低密度脂蛋白胆固醇与高密度脂蛋白胆固醇的比值、收缩压以及高血压病程的程度呈正相关。结论　颈动脉粥样硬化与冠状动脉粥样硬化的病变是平行的     

C反应蛋白与动脉粥样硬化的新进展

动脉粥样硬化是一种由于血管内皮功能紊乱或受损而引发的慢性炎症性疾病.目前认为,Ross[1]的"炎症假说"是动脉粥样硬化(atherosclerosis,AS)的主要发病机制,临床上可表现为脂质沉积、炎症细胞浸润、泡沫细胞形成、斑块的纤维化及钙化等[2].     

Shifting transition states in the unfolding of a large ankyrin repeat protein

The 33-amino-acid ankyrin motif comprises a beta-turn followed by two anti-parallel alpha-helices and a loop and tandem arrays of the motif pack in a linear fashion to produce elongated structures characterized by short-range interactions. In this article we use site-directed mutagenesis to investigate the kinetic unfolding mechanism of D34, a 426-residue, 12-ankyrin repeat fragment of the protein ankyrinR. The data are consistent with a model in which the N-terminal half of the protein unfolds first by unraveling progressively from the start of the polypeptide chain to form an intermediate; in the next step, the C-terminal half of the protein unfolds via two pathways whose transition states have either the early or the late C-terminal ankyrin repeats folded. We conclude that the two halves of the protein unfold by different mechanisms because the N-terminal moiety folds and unfolds in the context of a folded C-terminal moiety, which therefore acts as a "seed" and confers a unique directionality on the process, whereas the C-terminal moiety folds and unfolds in the context of an unfolded N-terminal moiety and therefore behaves like a single-domain ankyrin repeat protein, having a high degree of symmetry and consequently more than one unfolding pathway accessible to it.     

An experimentally determined protein folding energy landscape

Energy landscapes have been used to conceptually describe and model protein folding but have been difficult to measure experimentally, in large part because of the myriad of partly folded protein conformations that cannot be isolated and thermodynamically characterized. Here we experimentally determine a detailed energy landscape for protein folding. We generated a series of overlapping constructs containing subsets of the seven ankyrin repeats of the Drosophila Notch receptor, a protein domain whose linear arrangement of modular structural units can be fragmented without disrupting structure. To a good approximation, stabilities of each construct can be described as a sum of energy terms associated with each repeat. The magnitude of each energy term indicates that each repeat is intrinsically unstable but is strongly stabilized by interactions with its nearest neighbors. These linear energy terms define an equilibrium free energy landscape, which shows an early free energy barrier and suggests preferred low-energy routes for folding.     

p38MAPK、CARP在间歇低氧大鼠心肌重塑中的作用

目的 通过构建间歇低氧大鼠模型,检测模型大鼠心肌肥厚指数、心肌组织中p38MAPK、心锚重复蛋白(CARP)蛋白表达量的变化,探讨间歇低氧对心肌重塑的影响.方法 选取健康雄性SD大鼠24只,随机分3组:间歇低氧8周组(IH8)、间歇低氧4周组(IH4)、常氧组(NC)每组8只.测定各组体质量、左心室质量及左室肥厚指数;用免疫组织化学法测定各组心肌组织p38MAPK、CARP蛋白含量,并做HE染色,观察各组心肌组织形态学变化.结果 与NC组大鼠相比,IH4、IH8组大鼠心肌肥厚指数增加,IH8组更为明显(P＜0.05);IH8、IH4组p38MAPK、CARP蛋白表达均较NC组增加,IH8组较IH4组更为明显(P＜0.001);HE染色结果显示IH4、IH8组心肌细胞排列紊乱,IH8组更为明显.结论 间歇低氧与心肌重塑密切相关,p38MAPK通路与CARP的表达上调可能是其发生机制之一.     

Structural insights into an equilibrium folding intermediate of an archaeal ankyrin repeat protein

Repeat proteins are widespread in nature, with many of them functioning as binding molecules in protein-protein recognition. Their simple structural architecture is used in biotechnology for generating proteins with high affinities to target proteins. Recent folding studies of ankyrin repeat (AR) proteins revealed a new mechanism of protein folding. The formation of an intermediate state is rate limiting in the folding reaction, suggesting a scaffold function of this transient state for intrinsically less stable ARs. To investigate a possible common mechanism of AR folding, we studied the structure and folding of a new thermophilic AR protein (tANK) identified in the archaeon Thermoplasma volcanium. The x-ray structure of the evolutionary much older tANK revealed high homology to the human CDK inhibitor p19(INK4d), whose sequence was used for homology search. As for p19(INK4d), equilibrium and kinetic folding analyses classify tANK to the family of sequential three-state folding proteins, with an unusual fast equilibrium between native and intermediate state. Under equilibrium conditions, the intermediate can be populated to >90%, allowing characterization on a residue-by-residue level using NMR spectroscopy. These data clearly show that the three C-terminal ARs are natively folded in the intermediate state, whereas native cross-peaks for the rest of the molecule are missing. Therefore, the formation of a stable folding unit consisting of three ARs is the necessary rate-limiting step before AR 1 and 2 can assemble to form the native state.     

幽门螺杆菌毒力因子CagA与动脉粥样硬化

幽门螺杆菌的毒力因子CagA在动脉粥样硬化发病机制中起重要作用,CagA阳性的Hp感染能增加动脉粥样硬化的危险度,并通过抗原模拟、诱导自身免疫反应以及增强全身或动脉局部的炎症反应等途径促进动脉粥样硬化的发生发展。