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61.
《Expert opinion on therapeutic targets》2013,17(6):735-749
Soluble guanylate cyclase (sGC) is a heterodimeric haemoprotein, which represents the intracellular receptor for the ubiquitous biological messenger nitric oxide (NO). Activation of the enzyme facilitates conversion of GTP to the intracellular second messenger cGMP, and it is this molecule which mediates the majority of biological actions attributed to NO. sGC is expressed in virtually all mammalian cells and is important in mediating numerous physiological processes, including vascular and non-vascular smooth muscle relaxation, peripheral and central neurotransmission, platelet reactivity and phototransduction. Due to its ubiquitous nature, the pathogenesis of various disease states has been linked to aberrations in sGC signalling. This is especially true of the cardiovascular system, where inappropriate activation of sGC may underlie conditions such as stroke, atherosclerosis, impotence and septic shock; however, altered sGC activation has also been associated with the pathogenesis of asthma and certain neurodegenerative disorders. Therefore, agents that can modulate sGC function selectively will have considerable therapeutic potential, particularly in the treatment of cardiovascular disease. 相似文献
62.
Naofumi Ikeda Toshihide Hayashi Shikou Gen Nobuhiko Joki Kazuhiko Aramaki 《Renal failure》2022,44(1):1098
PurposeTo determine the location of coronary atherosclerosis distribution observed in patients with chronic kidney disease (CKD).MethodsA cross-sectional study was conducted using the database of cardiovascular medicine data from Saitama Sekishinkai Hospital to clarify the association between renal function and angiographic characteristics of coronary atherosclerosis. In total, 3268 patients who underwent percutaneous coronary intervention were included. Propensity score matching revised the total to 1772. The association of renal function with the location and/or distribution of coronary atherosclerosis lesions was then examined.ResultsOverall, coronary lesion was observed in the left anterior descending coronary artery (LAD) in 56% patients, whereas 28% and 22% were in the right coronary artery (RCA) and left circumflex coronary artery (LCX), respectively. LAD was most affected and observed in 57% patients with stage 1 CKD. RCA was second-most affected, at 26% CKD stage 1, but it increased to 31%, 38%, and 59% in CKD 3, 4, and 5, respectively. In CKD 5 patients, the RCA was the most affected artery (59%), with 41% LAD lesions. Logistic regression analysis after propensity score matching showed that the odds ratios for an RCA lesion was 3.658 in CKD 5 (p = .025) compared with CKD 1 after adjusting for traditional risk factors.ConclusionThe prevalence of RCA lesions, but not LAD or LCX lesions, increased with increasing CKD stage. The pathophysiology of coronary atherosclerosis may differ by lesion location. Deterioration of renal function may affect progression of atherosclerosis more in the RCA than in the LAD or LCX. 相似文献
63.
阻塞性睡眠呼吸暂停低通气综合征是心血管疾病的独立危险因素,严重影响患者的生命质量和生存时间,也是可以改变的心血管疾病危险因素之一。动脉粥样硬化是造成心血管疾病的病理基础,而大量研究发现阻塞性睡眠呼吸暂停低通气综合征与亚临床动脉粥样硬化相关,综述阻塞性睡眠呼吸暂停低通气综合征与亚临床动脉粥样硬化的研究进展,并梳理其中发病机制,为阻塞性睡眠呼吸暂停低通气综合征患者动脉粥样硬化的预防和早期干预提供依据。 相似文献
64.
脂蛋白脂酶活化剂NO-1886抑制糖尿病兔动脉粥样硬化的形成 总被引:3,自引:2,他引:3
目的 合成化合物NO 1886 ,一种脂蛋白脂酶活化观察脂蛋白脂酶活化剂是否降低高脂 /高蔗糖饲料诱发的糖尿病新西兰兔的血浆葡萄糖并减轻其动脉粥样硬化。方法 给予高脂 /高蔗糖饲料升高新西兰兔血浆总胆固醇 ,甘油三酯和葡萄糖及降低高密度脂蛋白胆固醇而导致动脉粥样硬化。饲料中加入 1 0 %NO 1886进行治疗观察。分别在 0、4、8、12、16、2 0及 2 4wk从禁食过夜的兔耳静脉抽取血样测定葡萄糖和脂质水平。第 2 4周末 ,处死动物 ,分离主动脉 ,经苏丹Ⅳ染色固定脂质后 ,计算脂纹病变面积。结果 应用NO 1886后 ,实验动物血浆葡萄糖 ,总胆固醇和甘油三酯降低 ,高密度脂蛋白胆固醇增加。对动脉粥样硬化的发展具有抑制作用。结论 NO 1886不仅可改善脂质紊乱 ,而且可降低血浆葡萄糖 ,减轻糖尿病兔动脉粥样硬化 相似文献
65.
Aim: Paeonol (2'-hydroxy-4'-methoxyacetophenone) from Cortex moutan root is a potential therapeutic agent for atherosclerosis. This study sought to investigate the mechanisms underlying anti-inflammatory effects of paeonol in rat vascular endothelial cells (VECs) in vitro.
Methods: VECs were isolated from rat thoracic aortas. The cells were pretreated with paeonol for 24 h, and then stimulated with ox-LDL for another 24 h. The expression of microRNA-21 (miR-21) and PTEN in VECs was analyzed using qRT-PCR. The expression of PTEN protein was detected by Western blotting. TNF-α release by VECs was measured by ELISA.
Results: Ox-LDL treatment inhibited VEC growth in dose- and time-dependent manners (the value of IC50 was about 20 mg/L at 24 h). Furthermore, ox-LDL (20 mg/L) significantly increased miR-21 expression and inhibited the expression of PTEN, one of downstream target genes of miR-21 in VECs. In addition, ox-LDL (20 mg/L) significantly increased the release of TNF-α from VECs. Pretreatment with paeonol increased the survival rate of ox-LDL-treated VECs in dose- and time-dependent manners. Moreover, paeonol (120 μmol/L) prevented ox-LDL-induced increases in miR-21 expression and TNF-α release, and ox-LDL-induced inhibition in PTEN expression. A dual-luciferase reporter assay showed that miR-21 bound directly to PTEN's 3'-UTR, thus inhibiting PTEN expression. In ox-LDL treated VECs, transfection with a miR-21 mimic significantly increased miR-21 expression and inhibited PTEN expression, and attenuated the protective effects of paeonol pretreatment, whereas transfection with an miR-21 inhibitor significantly decreased miR-21 expression and increased PTEN expression, thus enhanced the protective effects of paeonol pretreatment.
Conclusion: miR-21 is an important target of paeonol for its protective effects against ox-LDL-induced VEC injury, which may play critical roles in development of atherosclerosis. 相似文献
Methods: VECs were isolated from rat thoracic aortas. The cells were pretreated with paeonol for 24 h, and then stimulated with ox-LDL for another 24 h. The expression of microRNA-21 (miR-21) and PTEN in VECs was analyzed using qRT-PCR. The expression of PTEN protein was detected by Western blotting. TNF-α release by VECs was measured by ELISA.
Results: Ox-LDL treatment inhibited VEC growth in dose- and time-dependent manners (the value of IC50 was about 20 mg/L at 24 h). Furthermore, ox-LDL (20 mg/L) significantly increased miR-21 expression and inhibited the expression of PTEN, one of downstream target genes of miR-21 in VECs. In addition, ox-LDL (20 mg/L) significantly increased the release of TNF-α from VECs. Pretreatment with paeonol increased the survival rate of ox-LDL-treated VECs in dose- and time-dependent manners. Moreover, paeonol (120 μmol/L) prevented ox-LDL-induced increases in miR-21 expression and TNF-α release, and ox-LDL-induced inhibition in PTEN expression. A dual-luciferase reporter assay showed that miR-21 bound directly to PTEN's 3'-UTR, thus inhibiting PTEN expression. In ox-LDL treated VECs, transfection with a miR-21 mimic significantly increased miR-21 expression and inhibited PTEN expression, and attenuated the protective effects of paeonol pretreatment, whereas transfection with an miR-21 inhibitor significantly decreased miR-21 expression and increased PTEN expression, thus enhanced the protective effects of paeonol pretreatment.
Conclusion: miR-21 is an important target of paeonol for its protective effects against ox-LDL-induced VEC injury, which may play critical roles in development of atherosclerosis. 相似文献
66.
兔颈动脉狭窄模型的建立 总被引:1,自引:0,他引:1
目的寻求一个家兔颈动脉粥样硬化模型的简单、重复性好的方法。方法利用双氧水化学烧灼12只、大白兔颈动脉内膜,并分别在术后3 d、1周、4周行DSA检查,观察颈动脉狭窄模型的动态变化。结果成功获得颈动脉狭窄模型。结论本方法可以建立一种成熟的颈动脉粥样硬化模型,而且此方法简单、重复性好,有利于进行颈动脉粥样硬化的实验研究。 相似文献
67.
目的探讨脑梗死患者颈动脉粥样硬化性斑块与超敏C-反应蛋白(Hs-CRP)含量的关系。方法分别测定30名通过颈动脉超声检查发现有粥样硬化斑块的急性脑梗死(A组)、脑供血不足患者(B组)和无颈动脉粥样硬化斑块老年健康体检者(C组)血清中Hs-CRP含量。结果A组Hs-CRP含量明显高于B组和C组(P〈0.05);而B组和C组之间无显著性差异。结论Hs-CRP与动脉硬化引起的急性脑梗死有关,Hs-CRP与稳定性颈动脉硬化性斑块患者的脑供血不足的症状无关。 相似文献
68.
2型糖尿病患者血尿酸水平与尿白蛋白排泄率及颈动脉内中膜厚度的关系 总被引:1,自引:0,他引:1
目的 探讨2型糖尿病(T2DM)患者血清尿酸(SUA)水平与尿白蛋白排泄率(UAER)和颈动脉内中膜厚度(CIMT)的关系.方法 2008年5月-2009年5月收治T2DM患者372例,其中男性184例,女性188例.收集相关临床资料.Pearson法检验患者SUA水平与各项临床指标的相关性;多元逐步回归法分析影响UAER和CIMT的相关因素.结果 男性T2DM患者SUA水平明显高于女性(P<0.01).男性和女性T2DM患者SUA水平均与UAER相关;在校正内生肌酐清除率(Ccr)的影响后,相关性仍然存在(男性:r=0.24, P<0.01;女性:r=0.29, P<0.01).女性T2DM患者SUA水平与CIMT相关(r=0.29, P<0.01). 多元逐步回归分析显示,SUA是T2DM患者UAER(男性: β=0.16,P<0.05;女性: β=0.20,P<0.05)及女性T2DM患者CIMT的独立相关因素(β=0.16,P<0.05).结论 SUA在T2DM患者肾病和心血管病的发生和发展中起一定作用,控制SUA水平可能有助于延缓糖尿病肾病和防治糖尿病血管并发症. 相似文献
69.
70.
Objective: To investigate the effect of Qingre Quyu Granule (清热祛瘀颗粒, QRQYG) on stabilizing vulnerable plaques in apolipoprotein E (ApoE) defficient mice. Methods: Seventy-two male ApoE defficient mice were given a high-fat diet from 6 weeks of age. At the 16th week, all the mice were randomized into 3 groups: the QRQYG group, the simvastatin group, and the control group. Sixteen weeks after administration of 0.9 g/kg QRQYG, 3 mg/kg simvastatin or 10 mg/kg sodium chloride per day to the respective groups, the animals were euthanized. The pathological morphologic changes in the vulnerable plaques were evaluated, the matrix metalloprotease-9 (MMP-9) expression was measured by immunohistofluorescence, the soluble intercellular adhesion molecule 1 (ICAM-1) was determined by ELISA, the nuclear factor kappaB (NF-κB) subunit p65 was measured by quantitative RT-PCR, and, finally, thrombospondin-1 (TSP-1) was determined by the immunohistochemical method. Results: The plaque cross-sectional area in the brachiocephalic artery (23.7%, P0.01), the lipid core of the plaque (43.1%±3.1%), and the number of buried ?brotic caps of the plaque were significantly decreased in the QRQYG group compared to the control group (both P0.01); furthermore, the thickness of the ?brotic cap of the plaque increased and the intra-plaque hemorrhage of the plaque decreased. The serum soluble ICAM-1 (27.1±5.1 μg/mL), the protein expression of MMP-9 and TSP-1 and the p65 mRNA expression increased in the QRQYG group in comparison with the control group (P0.05 or P0.01). Conclusion: QRQYG could stabilize the vulnerable plaque through inhibition of the inflammatory response. 相似文献