Cocktail Therapy Combining SGLT2 Inhibitor, Entresto, and Adipose-Derived Mesenchymal Stem Cells Prevents Abdominal Aortic Aneurysmal Complication Syndrome in Rodents.

IF 1.9 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS

Acta Cardiologica Sinica Pub Date : 2026-09-01 DOI:10.6515/ACS.202609_42(5).20260101A

Jiunn-Jye Sheu, Han-Tan Chai, Yi-Ling Chen, Sheung-Fat Ko, Pei-Hsun Sung, Hon-Kan Yip

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引用次数: 0

Abstract

Background: This study investigated whether triple combination therapy [dapagliflozin (DAPA) + sacubitril/valsartan (Entresto) + adipose-derived mesenchymal stem cells (ADMSCs)] offered additional benefits on preventing complication syndrome [defined as abdominal aortic aneurysm (AAA) dilatation, muscle layer destruction and inflammation] in rodents with AAA.

Methods: Adult male Sprague-Dawley rats (n = 54) were equally categorized into group 1 (sham control), group 2 (AAA only), group 3 [AAA + DAPA (20 mg/kg/day orally from days 7 to 28 after AAA induction)], group 4 [AAA + Entresto (100 mg/kg/day orally from days 7 to 28 after AAA induction)], group 5 [AAA + ADMSCs (1.0 × 10⁶ cells) by intravenous administration from day 7 after AAA induction for 3 consecutive dosages at 3-day intervals)], and group 6 (AAA + combined DAPA-Entresto-ADMSCs).

Results: The results showed that the AAA diameter at day 28 was smallest in group 1, biggest in group 2, significantly larger in group 4 than in groups 3/5/6, and significantly larger in groups 4/5 than in group 6; however, there was no difference between groups 4 and 5 (all p < 0.0001). Light microscopic findings demonstrated that the AAA intimal thickness (i.e., indicator of intimal hyperplasia)/fibrotic area/number of immune-inflammatory [cluster of differentiation (CD) 3+/CD4+/matrix metalloproteinase [MMP] 2+/MMP9+] cells displayed an identical pattern, whereas the integrity of the laminar structure of AAA medial-muscle layer/number of small vessels exhibited an opposite pattern of AAA diameter among the groups (all p < 0.0001). The protein expressions of inflammation (tumor necrosis factor-alpha/interleukin (IL)-1 beta/IL-6/MMP2/MMP9)/fibrosis (transforming growth factor-beta/mothers against decapentaplegic homolog 3) markers displayed an identical pattern, whereas the protein expressions of tissue inhibitors of metalloproteinases (tissue inhibitor of metalloproteinases-1/tissue inhibitor of metalloproteinases-2) and apoptosis (cleaved-Caspase3/cleaved-poly(ADP-ribose) polymerase) displayed an opposite pattern of AAA diameter among the groups (all p < 0.0001).

Conclusions: The results of the present study support that triple therapy with DAPA + Entresto + ADMSCs could be an innovative therapeutic modality for AAA.

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联合SGLT2抑制剂、enterresto和脂肪源间充质干细胞的鸡尾酒疗法预防啮齿类动物腹主动脉瘤并发症综合征

背景：本研究探讨了三联疗法[达格列清(DAPA) +沙比里尔/缬沙坦(enterresto) +脂肪源性间充质干细胞（ADMSCs）]是否能在预防AAA啮齿动物并发症综合征(定义为腹主动脉瘤（AAA）扩张、肌肉层破坏和炎症]方面提供额外的益处。成年男性Sprague-Dawley老鼠(n = 54)也同样分为组1(虚假的控制),组2只(AAA),组3 [AAA +防卫事业厅(20毫克/公斤/天口头AAA感应后从7天到28)],组4 [AAA + Entresto(100毫克/公斤/天口头AAA感应后从7天到28)],集团5 [AAA + ADMSCs(1.0×106个细胞),静脉注射后第七天AAA感应连续3剂量每隔三天),和组6 (AAA +结合DAPA-Entresto-ADMSCs)。结果：第28天的AAA直径以1组最小，2组最大，4组显著大于3/5/6组，4/5组显著大于6组；然而，第4组和第5组之间没有差异（p < 0.0001）。光镜检查结果显示，各组间AAA级内膜厚度（即内膜增生指标）/纤维化面积/免疫炎性[cd3 +/CD4+/基质金属蛋白酶[MMP] 2+/MMP9+]细胞数量表现出相同的模式，而AAA级内肌层层状结构的完整性/小血管数量表现出与AAA级直径相反的模式（均p < 0.0001）。炎症（肿瘤坏死因子- α /白细胞介素(IL)-1 β /IL-6/MMP2/MMP9）/纤维化（转化生长因子- β /母亲抗十肢瘫痪同源物3）标志物的蛋白表达模式相同；而金属蛋白酶组织抑制剂（metalloproteinases的组织抑制剂-1/ metalloproteinases的组织抑制剂-2）和凋亡（caspase3 / adp -核糖）的蛋白表达与AAA直径相反（均p < 0.0001）。结论：本研究结果支持DAPA + Entresto + ADMSCs三联疗法可能是AAA的一种创新治疗方式。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Cardiologica Sinica 医学-心血管系统

CiteScore

2.90

自引率

15.80%

发文量

144

审稿时长

>12 weeks

期刊介绍： Acta Cardiologica Sinica welcomes all the papers in the fields related to cardiovascular medicine including basic research, vascular biology, clinical pharmacology, clinical trial, critical care medicine, coronary artery disease, interventional cardiology, arrythmia and electrophysiology, atherosclerosis, hypertension, cardiomyopathy and heart failure, valvular and structure cardiac disease, pediatric cardiology, cardiovascular surgery, and so on. We received papers from more than 20 countries and areas of the world. Currently, 40% of the papers were submitted to Acta Cardiologica Sinica from Taiwan, 20% from China, and 20% from the other countries and areas in the world. The acceptance rate for publication was around 50% in general.