Background Thoracic aortic endovascular repair (TEVAR) of uncomplicated type B aortic dissection (uTBAD) has favorable long-term outcomes but higher early adverse events compared with the optimal medical treatment. Recently, clinical evidence concerning vascular surgery indicates that elevated preoperative systemic inflammatory response predicts adverse clinical events. The aim of our study was to evaluate the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR) and early outcomes of uTBAD patients undergoing TEVAR. Results 216 patients diagnosed with uTBAD were included in this retrospective study between January 2015 and December 2018. The median (IQR) follow-up period was 21 (15–33) months. An early adverse event was defined as occurring within 2 years after the procedure. Median patient age was 60 (IQR, 48–68) years and 78.7 % were male. Early adverse events occurred in 24 patients (11.1 %). In the multivariable analysis, preoperative NLR (HR per SD, 1.98; 95 % CI, 1.14–3.44; P = 0.015) was associated with 2-year adverse events. Conclusions NLR is an independent predictive factor of early adverse events in uTBAD patients undergoing TEVAR.
Background Increasing evidence indicates that myocardial oxidative injury plays a crucial role in the pathophysiology of cardiac hypertrophy (CH) and heart failure (HF). The active component of rhubarb, rhein exerts significant actions on oxidative stress and inflammation. Nonetheless, its role in cardiac remodeling remains unclear. Methods CH was induced by angiotensin II (Ang II, 1.4 mg/kg/d for 4 weeks) in male C57BL/6 J mice. Then, rhein (50 and 100 mg/kg) was injected intraperitoneally for 28 days. CH, fibrosis, oxidative stress, and cardiac function in the mice were examined. In vitro, neonatal rat cardiomyocytes (CMs) and cardiac fibroblasts (CFs) pre-treated with rhein (5 and 25 μM) were challenged with Ang II. We performed RNA sequencing to determine the mechanistic role of rhein in the heart. Results Rhein significantly suppressed Ang II-induced CH, fibrosis, and reactive oxygen species production and improved cardiac systolic dysfunction in vivo. In vitro, rhein significantly attenuated Ang II-induced CM hypertrophy and CF collagen expression. In addition, rhein obviously alleviated the increased production of superoxide induced by Ang II. Mechanistically, rhein inhibited FGF23 expression significantly. Furthermore, FGF23 overexpression abolished the protective effects of rhein on CMs, CFs, and cardiac remodeling. Rhein reduced FGF23 expression, mostly through the activation of AMPK (AMP-activated protein kinase). AMPK activity inhibition suppressed Ang II-induced CM hypertrophy and CF phenotypic transformation. Conclusion Rhein inhibited Ang II-induced CH, fibrosis, and oxidative stress during cardiac remodeling through the AMPK–FGF23 axis. These findings suggested that rhein could serve as a potential therapy in cardiac remodeling and HF.
Background Stent-graft-induced inflammation is an independent risk factor for adverse aortic remodeling in aortic dissection. In this context, we asked that whether a methylprednisolone-loaded stent-graft could reduce inflammation and degradation. Methods First, a coaxial electrospinning technique was used to create a core-shell film with methylprednisolone encapsulated in the inner of poly (L-lactide-co-caprolactone) nanofibers for controllable drug release. Second, an in vitro study was conducted to evaluate the biocompatibility of the nanofiber meshes. Third, the porcine aortic dissection model was developed to investigate the therapeutic effects of the methylprednisolone-loaded stent-graft. Results The results demonstrated that the nanofiber-coated film with a methylprednisolone-poly-caprolactone core layer and a poly (L-lactide-co-caprolactone) shell layer could effectively sustain drug release in vitro. In vivo study showed that the methylprednisolone-loaded stent-graft could reduce degradtion of aortic dissection by regulating inflammation. Conclusions Overall, the controllable drug release by coaxial nanofiber is a promising approach to alleviate aortic inflammation and promote aortic remodeling after stent-graft implantation.
Abdominal aortic aneurysm (AAA) represents the serious vascular degenerative disorder, which causes high incidence and mortality. Alpha-ketoglutarate (AKG), a crucial metabolite in the tricarboxylic acid (TCA) cycle, has been reported to exert significant actions on the oxidative stress and inflammation. However, its role in AAA still remains elusive. Herein, we examined the effects of AKG on the formation of AAA. The study established an elastase-induced mouse abdominal aortic aneurysms model as well as a TNF-α-mediated vascular smooth muscle cells (VSMCs) model, respectively. We displayed that AKG pre-treatment remarkably prevented aneurysmal dilation assessed by diameter and volume and reduced aortic rupture. In addition, it was also observed that AKG treatment suppressed the development of AAA by attenuating the macrophage infiltration, elastin degradation and collagen fibers remodeling. In vitro, AKG potently decreased TNF-α-induced inflammatory cytokines overproduction, more apoptotic cells and excessive superoxide. Mechanistically, we discovered that upregulation of vpo1 in AAA was significantly suppressed by AKG treatment. By exploring the RNA-seq data, we found that AKG ameliorates AAA mostly though inhibiting oxidative stress and the inflammatory response. PXDN overexpression neutralized the inhibitory effects of AKG on ROS generation and inflammatory reaction in MOVAS. Furthermore, AKG treatment suppressed the expression of p-ERK1/2, 3-Cl Tyr in vivo and in vitro. ERK activator disrupted the protective of AKG on TNF-α-induced VSMCs phenotypic switch. Conclusively, AKG can serve as a beneficial therapy for AAA through regulating PXDN/HOCL/ERK signaling pathways.
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