Interplay of oxidative, nitrosative/nitrative stress, inflammation, cell death and autophagy in diabetic cardiomyopathy.
Interplay of oxidative, nitrosative/nitrative stress, inflammation, cell death and autophagy in diabetic cardiomyopathy.
复制标题
DOI：
10.1016/j.bbadis.2014.06.030
复制
发表时间：
2015-02
影响因子：
6.2
通讯作者：
Pacher, Pal
中科院分区：
文献类型：
--
作者：
Varga, Zoltan V.;Giricz, Zoltan;Liaudet, Lucas;Hasko, Gyoergy;Ferdinandy, Peter;Pacher, Pal
糖尿病是公认的心血管疾病和心力衰竭的危险因素。糖尿病心血管功能障碍还强调了糖尿病视网膜病变、肾病和神经病变的发展。尽管抗糖尿病治疗已得到广泛应用，但血糖控制仍然是糖尿病患者管理中的主要挑战。高血糖会触发高级糖基化终产物 (AGE) 的形成，激活蛋白激酶 C，增强多元醇途径、葡萄糖自氧化（与游离脂肪酸水平升高相结合），而瘦素则与糖尿病脉管系统中线粒体、NADPH 氧化酶和黄嘌呤氧化还原酶产生的超氧阴离子增加有关。 心肌。超氧阴离子与一氧化氮相互作用，通过扩散限制反应形成强效毒素过氧亚硝酸盐，与其他氧化剂一起触发应激激酶的激活、内质网应激、线粒体和聚（ADP-核糖）聚合酶 1 依赖性细胞死亡、调节自噬/线粒体自噬、失活参与自噬的关键蛋白。 心肌钙处理/收缩性和抗氧化防御，激活基质金属蛋白酶和氧化还原依赖性促炎转录因子（例如核因子 kappaB），促进炎症、AGE 形成，最终导致心肌功能障碍、重塑和心力衰竭。了解氧化/亚硝化应激与促炎、代谢和细胞死亡途径之间复杂的相互作用对于设计糖尿病心肌病的新型靶向疗法至关重要，本简要概述将对此进行概述。
Diabetes is a recognized risk factor for cardiovascular diseases and heart failure. Diabetic cardiovascular dysfunction also underscores the development of diabetic retinopathy, nephropathy and neuropathy. Despite the broad availability of antidiabetic therapy, glycaemic control still remains a major challenge in the management of diabetic patients. Hyperglycaemia triggers formation of advanced glycosylation end products(AGEs), activates protein kinase C, enhances polyol pathway, glucose autoxidation, which coupled with elevated levels of free fatty acids, and leptin have been implicated in increased generation of superoxide anion by mitochondria, NADPH oxidases and xanthine oxidoreductase in diabetic vasculature and myocardium. Superoxide anion interacts with nitric oxide forming the potent toxin peroxynitrite via diffusion limited reaction, which in concert with other oxidants triggers activation of stress kinases, endoplasmic reticulum stress, mitochondrial and poly(ADP-ribose) polymerase 1-dependent cell death, dysregulates autophagy/mitophagy, inactivates key proteins involved in myocardial calcium handling/contractility and antioxidant defense, activates matrix metalloproteinases and redox-dependent pro-inflammatory transcription factors (e.g. nuclear factor kappaB) promoting inflammation, AGEs formation, eventually culminating in myocardial dysfunction, remodeling and heart failure. Understanding the complex interplay of oxidative/nitrosative stress with pro-inflammatory, metabolic and cell death pathways is critical to devise novel targeted therapies for diabetic cardiomyopathy, which will be overviewed in this brief synopsis.
登录
查看更多内容
影响因子：
9.3
作者：
Al-Attas OS;Al-Daghri NM;Al-Rubeaan K;da Silva NF;Sabico SL;Kumar S;McTernan PG;Harte AL
通讯作者：
Harte AL
影响因子：
29
作者：
Bai P;Canto C;Brunyánszki A;Huber A;Szántó M;Cen Y;Yamamoto H;Houten SM;Kiss B;Oudart H;Gergely P;Menissier-de Murcia J;Schreiber V;Sauve AA;Auwerx J
通讯作者：
Auwerx J
影响因子：
8
作者：
Altenhofer, Sebastian;Kleikers, Pamela W. M.;Radermacher, Kim A.;Scheurer, Peter;Hermans, J. J. Rob;Schiffers, Paul;Ho, Heidi;Wingler, Kirstin;Schmidt, Harald H. H. W.
通讯作者：
Schmidt, Harald H. H. W.
影响因子：
4.8
作者：
Aroor, Annayya R.;Sowers, James R.;DeMarco, Vincent G.
通讯作者：
DeMarco, Vincent G.
DOI：
10.1152/ajpregu.00423.2010
发表时间：
2011-02-01
影响因子：
2.8
作者：
Baseler, Walter A.;Dabkowski, Erinne R.;Hollander, John M.
通讯作者：
Hollander, John M.