Sleeve Gastrectomy Provides Cardioprotection from Oxidative Stress In Vitro Due to Reduction of Circulating Myeloperoxidase.
Sleeve Gastrectomy Provides Cardioprotection from Oxidative Stress In Vitro Due to Reduction of Circulating Myeloperoxidase.
复制标题
DOI：
10.3390/nu15224776
复制
发表时间：
2023-11-14
期刊：
影响因子：
5.9
通讯作者：
Kindel TL
中科院分区：
文献类型：
--
作者：
Barron M;Hayes H;Bice Z;Pritchard K;Kindel TL
在啮齿动物模型中，减肥手术，包括袖状胃切除术(SG)，可以改善收缩和舒张期功能，这与体重减轻无关。独立于体重减轻的心功能改善的原因尚不清楚，但可能源于胃肠道。在这项研究中，我们通过测试啮齿类动物SG血浆在体外降低代谢应激的有效性来研究循环血液因子是否是SG后急性心脏保护的机制。在最初的实验中，肥胖的雄性Zucker大鼠接受了SG、即兴假手术或成对喂养的假手术(n=6个SG，n=8个SH，n=8个PF)。在所有其他研究中，第二组Zucker大鼠接受SG或即刻假手术(n=8 SH，n=6 SG)。手术后6周，分别在空腹和餐后(Pp)状态下收集各组的血浆。然后将这些血浆按手术组和营养状态混合，并在多个体外细胞培养和细胞外检测中进行测试，以确定与假手术组相比，SG对肌管代谢性应激的影响。餐后SG血浆(PPSG)，而不是空腹SG、PP或空腹假血浆，通过乳酸脱氢酶(LDH)释放来降低H9c2细胞的代谢应激(p<；0.01)。与SG不同的是，通过配对喂养的体重减轻并不能防止H9c2代谢应激。与pp Sham组、空腹SG组和空腹Sham组相比，PPSG血浆的细胞外过氧化氢消耗速率和过氧化氢活性最慢。用氨基苯甲酸肼和依达拉奉对血浆进行氧化还原测试表明，髓过氧化物酶(MPO)或其他过氧化物酶是降低PPSG血浆代谢应激的主要成分。与PP Sham和空腹SG血浆相比，PPSG血浆中循环MPO蛋白的含量减少了35%。与西药对照组血浆中乳酸脱氢酶的显著增加相比，MPO基因敲除大鼠的血浆也能预防H9c2细胞的代谢应激反应(p<；0.01)。MPO全局敲除血浆的细胞外过氧化氢消耗率和过氧化活性也与PPSG血浆相当。这些研究表明，SG改善心肌细胞功能的不依赖体重的机制之一可能是由于循环中MPO水平的降低而减少了有利于氧化的环境。胃肠道似乎对这些发现至关重要，因为SG大鼠只有在肠内营养刺激后MPO水平才会降低。如果这种手术效果在人类中得到证实，SG可能是一种针对多种疾病的独特外科治疗方法，这些疾病的发病机制包括炎症和氧化损伤，包括与肥胖相关的心力衰竭，但射血分数保持不变。
Bariatric surgery, including sleeve gastrectomy (SG), improves systolic and diastolic function, which is independent of weight loss in rodent models. The cause of weight loss-independent improvements in cardiac function are unknown but may originate from the gastrointestinal tract. In this study, we investigated whether a circulating blood factor is a mechanism for acute cardioprotection after SG by testing the utility of rodent SG plasma to reduce metabolic stress in vitro. For the initial experiment, obese male Zucker rats underwent SG, ad lib sham, or pair-fed sham surgeries (n = six SG, n = eight SH, n = eight PF). For all other studies, a second group of Zucker rats underwent SG or ad lib sham surgeries (n = eight SH, n = six SG). Six weeks following surgery, plasma was collected from each group, both in the fasting and post-prandial (pp) state. This plasma was then pooled per surgical group and nutrient state and tested in multiple in vitro cell culture and extra-cellular assays to determine the effect of SG on myotubular metabolic stress compared to the sham surgeries. Post-prandial SG plasma (ppSG), but not fasting SG, pp, or fasting sham plasma, reduced the metabolic stress of the H9c2 cells as measured by lactate dehydrogenase (LDH) release (p < 0.01). Unlike SG, weight reduction through pair-feeding did not prevent H9c2 metabolic stress. The PpSG plasma had the slowest rate of extracellular hydrogen peroxide consumption and peroxidatic activity compared to the pp sham, fasting SG, and fasting sham groups. Redox testing of plasma with aminiobenzoic acid hydrazide and edaravone suggested a pattern supporting myeloperoxidase (MPO), or other peroxidases, as the primary component responsible for reduced metabolic stress with ppSG plasma. The PpSG plasma contained 35% less circulating MPO protein as compared to the pp sham and fasting SG plasma. The plasma from an MPO global knockout rat also prevented metabolic stress of the H9c2 cells, compared to the significant increase in LDH release from the plasma of the WT controls (p < 0.01). The MPO global knockout plasma also had a rate of extracellular hydrogen peroxide consumption and peroxidatic activity comparable to the ppSG plasma. These studies suggest that one of the weight loss-independent mechanisms by which SG improves myocellular function could be a reduced pro-oxidative environment due to lower circulating levels of MPO. It appears that the gastrointestinal tract is of critical importance to these findings, as the MPO levels were only lowered after enteral, nutrient stimulation in the SG rats. If this surgical effect is confirmed in humans, SG may be a unique surgical treatment for multiple diseases with a pathogenesis of inflammation and oxidative damage, including obesity-associated heart failure with preserved ejection fraction.
登录
查看更多内容
影响因子：
37.8
作者：
Zakeri R;Chamberlain AM;Roger VL;Redfield MM
通讯作者：
Redfield MM
影响因子：
3.9
作者：
Vanhamme, Luc;Boudjeltia, Karim Zouaoui;Delporte, Cedric
通讯作者：
Delporte, Cedric
DOI：
10.1161/hhf.0b013e318291329a
发表时间：
2013-05
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Heidenreich PA;Albert NM;Allen LA;Bluemke DA;Butler J;Fonarow GC;Ikonomidis JS;Khavjou O;Konstam MA;Maddox TM;Nichol G;Pham M;Piña IL;Trogdon JG;American Heart Association Advocacy Coordinating Committee;Council on Arteriosclerosis, Thrombosis and Vascular Biology;Council on Cardiovascular Radiology and Intervention;Council on Clinical Cardiology;Council on Epidemiology and Prevention;Stroke Council
通讯作者：
Stroke Council
影响因子：
2.8
作者：
Tang, W. H. Wilson;Brennan, Marie-Luise;Hazen, Stanley L.
通讯作者：
Hazen, Stanley L.
影响因子：
2.9
作者：
Zamocky, Marcel;Jakopitsch, Christa;Obinger, Christian
通讯作者：
Obinger, Christian