Osteocalcin and atherosclerosis: A complex relationship

The relationship between OC and atherosclerosis in different clinical situations confirms the interplay that exists among bone cells and vascular system. The recently demonstrated effects of OC on glucose metabolism and visceral fat in healthy subjects and T2DM patients, contribute to the knowledge of the role of OC in the pathogenesis of cardiovascular disease.     

酮替芬对Wistar大鼠动脉粥样硬化的干预研究

目的观察酮替芬(Ket)对动脉粥样硬化形成的干预作用。方法将40只雄性Wistar大鼠随机分为4组,即A组[高脂+维生素D_3(VitD_3)]、B组[高脂+VitD_3+Ket]、C组[高脂+VitD_3+卵蛋白(OVA)]和D组(高脂+VitD_3+OVA+Ket)。A组常规建立动脉粥样硬化模型,C组在常规高脂的基础上加用OVA激活肥大细胞建立动脉粥样硬化模型,B、D两组分别在A、C组建立动脉粥样硬化的过程中给予Ket干预。实验完毕后,分别对A、B组以及C、D组斑块病理形态及斑块中肥大细胞的分布情况进行比较。结果 (1)A、C组动脉粥样硬化病理改变分别较B、D组为重,可见典型AS及不稳定AS改变;B、D组Ket药物干预达到预期效果;(2)动脉粥样硬化斑块中的肥大细胞分布密度A组比B组:5.00±1.41比2.88±1.25,P<0.05;C组比D组:8.00±1.29比5.86±2.03,P<0.05,差异均有统计学意义;(3)实验结束时测定大鼠血清白介素(IL)-6水平,A组比B组:(60.18±8.15)ng/L比(41.52±6.71)ng/L,P<0.05;C组比D组:(90.66±8.18)ng/L比(68.32±5.92)ng/L,P<0.05,差异均有统计学意义。结论高脂+VitD_3+OVA能够建立较为成熟、更符合人类动脉粥样硬化病理形态的大鼠模型;肥大细胞在动脉粥样硬化的形成中有着重要作用,是动脉粥样硬化形成的重要炎症细胞;全身性的肥大细胞活化对斑块形成有促进作用;Ket有抑制炎症因子活化的作用,对斑块形成及失稳定有预防作用。     

Dissecting the role of AMP-activated protein kinase in human diseases

AMP-activated protein kinase (AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes. Accompanying the application of genetic methods and a plethora of AMPK agonists, rapid progress has identified AMPK as an attractive therapeutic target for several human diseases, such as cancer, type 2 diabetes, atherosclerosis, myocardial ischemia/reperfusion injury and neurodegenerative disease. The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere. In the present review, we summarize and update the paradoxical role of AMPK implicated in the diseases mentioned above and put forward the challenge encountered. Thus it will be expected to provide important clues for exploring rational methods of intervention in human diseases.     

Anti-atherosclerotic action of GW9508 – Free fatty acid receptors activator – In apoE-knockout mice

BackgroundIn the past two decades, enhanced understanding of the biology of G-protein-coupled receptors (GPRs) has led to the identification of several such receptors as novel targets for free fatty acids (FFAs). Two GPRs, FFAR1 and FFAR4, have received special attention in the context of chronic inflammatory diseases, thanks to their anti-inflammatory activities.MethodsThe present study investigates the influence of prolonged treatment with GW9508 – agonist of FFAR1 and FFAR4 – on the development of atherosclerosis plaque in apoE-knockout mice, using morphometric and molecular methods.ResultsGW9508 administration has led to the reduction of atheroscletoric plaque size in an apoE-knockout mice model. Moreover, a FFAR1/FFAR4 agonist reduced the content of macrophages by almost 20%, attributed by immunohistochemical phenotyping to the pro-inflammatory M1-like activation state macrophages.ConclusionsProlonged administration of GW9508 resulted in significant amelioration of atherogenesis, providing evidence that the strategy based on macrophage phenotype switching toward an M2-like activation state via stimulation of FFAR1/FFAR4 receptors holds promise for a new approach to the prevention or treatment of atherosclerosis.     

Serum omentin-1, inflammation and carotid atherosclerosis in patients with non-diabetic chronic kidney disease

Abstract

Background and aim: Omentin-1 is suggested to affect inversely atherosclerosis (AS). Data about omentin-1 is limited to chronic kidney disease (CKD). Our aim was to examine omentin-1 in non-diabetic CKD patients who are not dialyzed and investigate its relationships with inflammation and carotid AS. Materials and Methods: We performed a cross-sectional study in 55 non-diabetic CKD patients and 30 healthy controls. Baseline clinical and laboratory data were obtained for all participants. Serum omentin-1 and interleukin-6 (IL-6) levels were measured according to the manufacturer’s instructions. Carotic plaque and intima-media thickness (IMT) were assessed by carotid ultrasonography. The homeostasis model assessment of insulin resistance index (HOMA-IR) was used to assess IR. Results: Omentin-1 and IL-6 levels in the patient group were found to be higher than the control group; the differences were statistically significant (p?=?0.01 and p?=?0.04, respectively). Carotid IMT(mean) was significantly higher in the patient group (p?=?0.01). Omentin-1 did not correlate with IL-6 and IMT in the patient group (p?=?0.51 and p?=?0.76, respectively). In subgroup analysis, omentin-1 levels in patients with carotid plaque were lower than those without carotid plaque (179.5?±?88.1?ng/ml and 185.9?±?67.8?ng/ml, respectively). However, the difference was not statistically significant (p?=?0.47). Conclusion: We conclude that omentin-1 is higher in not dialyzed non-diabetic CKD and there is no correlation between omentin-1 and IL-6 or carotid IMT(mean).     

Chlamydia pneumoniae and Atherosclerosis

Chlamydia pneumoniae, a human respiratory pathogen, has been linked to atherosclerotic disease based on sero-epidemiologic studies, direct detection of the organism in atherosclerotic lesions, animal experiments and tissue culture. In this review paper we propose to interprete results in line with the biology of Chlamydia with persistence of Chlamydia pneumoniae antigens in the pathogenesis of atherosclerosis rather than viable bacteriae.     

阿利吉仑与氨氯地平对肾动脉狭窄性大鼠斑块部位MMP9表达的比较研究

目的 选择一肾一夹（1K1C）、二肾一夹（2K1C）肾动脉狭窄性大鼠主动脉弓作为研究对象,比较阿利吉仑与苯磺酸氨氯地平对斑块部位基质金属蛋白酶9（MMP9）表达的影响.方法 将健康雄性SD大鼠随机分为对照组、1K1C组及2K1C组,行平行针灸针缩窄法造模及高脂饲养10周,生理盐水组：0.9% NS 2 ml/d、阿利吉仑组：50 mg/（kg·d）、苯磺酸氨氯地平组：6 mg/（kg·d）,4周后游离并切取SD大鼠主动脉弓,采用免疫组织化学法检测斑块部位MMP9的表达,Western-blot检测MMP9的表达.结果 1K1C及2K1C苯磺酸氨氯地平组与生理盐水组比较,其斑块部位MMP9的表达差异无统计学意义（P﹥0.05）;但阿利吉仑各组差异有统计学意义（P﹤0.05）.结论 苯磺酸氨氯地平对2K1C和1K1C大鼠斑块部位MMP9的表达无明显抑制作用,而阿利吉仑均可抑制各组斑块部位MMP9的表达,提示阿利吉仑稳定动脉粥样硬化斑块的作用可能优于苯磺酸氨氯地平.     

茯苓多糖对ApoE-/-AS小鼠肝脏脂质沉积及胆固醇逆向转运相关蛋白表达的影响＊

目的 探讨茯苓多糖对载脂蛋白E基因敲除（ApoE^-/-）动脉粥样硬化（Atherosclerosis，AS）小鼠肝脏脂质沉积及胆固醇逆向转运的影响。方法 采用随机数字表法将30只ApoE^-/-小鼠随机分为模型组、茯苓多糖组、辛伐他汀组，每组10只，10只C57BL/6J小鼠作为正常组。正常组给予基础饲料喂饲，其余小鼠给予高脂饲料喂饲12周。茯苓多糖组以0.2 g/kg/d灌胃，辛伐他汀组以2.275 mg/kg/天灌胃，正常组和模型组给予等体积生理盐水灌胃，共干预4周。全自动生化分析仪检测小鼠血清三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平，苏木素-伊红（HE）染色观察小鼠肝脏病理形态学变化，油红O染色观察小鼠肝脏脂质沉积情况，ELISA检测各组小鼠血清载脂蛋白A1 （ApoA1）、对氧磷酶-1（PON1）含量，Real-time RT-qPCR法及Western Blot法检测肝脏胆固醇酯转运蛋白（CETP）、磷脂转运蛋白（PLTP）、卵磷脂胆固醇酰基转移酶（LCAT）mRNA及蛋白表达。结果 与正常组比较，模型组小鼠血清TG、TC、LDL-C含量均明显上升，HDL-C含量明显下降（P<0.01），肝细胞脂肪变性明显，肝脏脂质沉积明显，小鼠血清ApoA1、PON1含量均明显下降（P<0.01），小鼠肝脏CETP、PLTP mRNA及蛋白表达明显上升，LCAT mRNA及蛋白表达明显下降（P<0.01）。与模型组相比，茯苓多糖组血清TG、TC、LDL-C含量均显著下降（P<0.01），HDL-C含量呈上升趋势（P>0.05），肝细胞脂肪变性、脂质沉积程度均有所减轻，茯苓多糖组ApoA1含量明显上升（P<0.01），PON1含量呈上升趋势（P>0.05），茯苓多糖组CETP、PLTP mRNA及蛋白表达有所下降，LCAT mRNA及蛋白表达有所上升（P<0.05，P<0.01）。结论 茯苓多糖可能通过调控血脂水平与胆固醇逆向转运过程，改善ApoE^-/- AS小鼠肝脏脂质沉积，进而发挥防治AS作用。