Ginsenoside Rb1 Ameliorates Diabetic Arterial Stiffening via AMPK Pathway

Background and Purpose: Macrovascular complication of diabetes mellitus, characterized by increased aortic stiffness, is a major cause leading to many adverse clinical outcomes. It has been reported that ginsenoside Rb1 (Rb1) can improve glucose tolerance, enhance insulin activity, and restore the impaired endothelial functions in animal models. The aim of this study was to explore whether Rb1 could alleviate the pathophysiological process of arterial stiffening in diabetes and its potential mechanisms.Experimental Approach: Diabetes was induced in male C57BL/6 mice by administration of streptozotocin. These mice were randomly selected for treatment with Rb1 (10−60 mg/kg, i. p.) once daily for 8 weeks. Aortic stiffness was assessed using ultrasound and measurement of blood pressure and relaxant responses in the aortic rings. Mechanisms of Rb1 treatment were studied in MOVAS-1 VSMCs cultured in a high-glucose medium.Key Results: Rb1 improved DM-induced arterial stiffening and the impaired aortic compliance and endothelium-dependent vasodilation. Rb1 ameliorated DM-induced aortic remodeling characterized by collagen deposition and elastic fibers disorder. MMP2, MMP9, and TGFβ1/Smad2/3 pathways were involved in this process. In addition, Rb1-mediated improvement of arterial stiffness was partly achieved via inhibiting oxidative stress in DM mice, involving regulating NADPH oxidase. Finally, Rb1 could blunt the inhibition effects of DM on AMPK phosphorylation.Conclusion and Implications: Rb1 may represent a novel prevention strategy to alleviate collagen deposition and degradation to prevent diabetic macroangiopathy and diabetes-related complications.

Development of a multi-arm polyrotaxanes modified mesoporous silica-coated gold nanoplatform for protecting endothelial progenitor cells against high glucose environment

Recent study reported that endothelial progenitor cells (EPCs) have potential to treat diabetic macroangiopathy. High glucose environment of diabetes can affect the adhesion of EPCs by decreasing the expression of CXC chemokine receptor 4 (CXCR4) and affect the proliferation of EPCs by decreasing the expression of miR-126. The results showed that the cytotoxicity of GNR@MSNs@PEI to EPCs was significantly lower than PEI; the temperature of GNR@MSNs@PEI solution can be controlled between 38–40°C under 808 nm laser irradiation. 25.67 µg of pcDNA3.1-GFP-CXCR4 and 5.36 µg of FITC-miR-126 could be loaded in 1 mg of GNR@MSNs@PEI; GNR@MSNs@PEI has gene transfection almost the same as Lipofectamine 3000. Subsequent in vitro studies showed that pcDNA3.1-GFP-CXCR4 and miR-126 loaded GNR@MSNs@PEI can significantly increase the adhesion and proliferation and decrease the apoptosis of EPCs treated with high glucose under 808 nm laser irradiation. In conclusion, nano-carriers (GNR@MSNs@PEI) with high pcDNA3.1-CXCR4 and miR-126 loading capacity, high biocompatibility, well cell internalization, and controllable release ability were constructed to transfer CXCR4 expression plasmid (pcDNA3.1-CXCR4) and miR-126 into EPCs efficiently. Further in vitro studies indicated that pcDNA3.1-CXCR4 and miR-126-loaded GNR@MSNs@PEI could protect EPCs against high glucose-induced injury.

Leeches alleviates diabetic macroangiopathy by increasing nitric oxide production in rat aorta and restoring endothelium-dependent vasodilatation

IntroductionDiabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose level over a prolonged period, leading to severe damage in tissues including the heart, blood vessels, eyes and the kidneys. Danzhi Jiangtang Capsule (DJC) is an effective drug for diabetes, but the mechanism responsible for its efficacy remains unknown. This study aimed to explore the effective ingredient of DJC that ameliorated diabetes and the possible mechanisms.Material and methodsWe orally treated streptozotocin (STZ)-induced diabetic rats with 540 mg/kg DIC or the same dose of its four active components, namely Leeches, Pseudostellaria Polysaccharides (PP), Paeonia Suffruticosa Andr (PSA) and Rehmannia Glutinosa Libosch (RGL), respectively for 8 weeks.ResultsAlthough all of these components could reduce blood glucose levels in diabetic rats, the extent of alleviation of DJC was more pronounced than all of its four ingredients. Unlike the other three components, Leeches is the only effective ingredient of DJC that decreased tetrahydrobiopterin (BH4) oxidation to activate endothelial nitric oxide synthase (eNOS), and increased nitric oxide (NO) production, leading to improved endothelium-dependent relaxation both in diabetic rats and in immortalized human mesangial cells under the stimulation of high glucose.ConclusionsLeeches could alleviate diabetic macroangiopathy by inhibiting NO release in endothelial cells under high-glucose condition.

Characterization of lncRNA and mRNA profiles in rats with diabetic macroangiopathy

Diabetic macroangiopathy is part of the most common serious complications of diabetes. Previous studies indicate that lncRNAs involved in the process of diabetes and another vascular disease. However, their detailed mechanism of the lncRNAs involved in diabetic macroangiopathy has not been well characterized. In the present study, we generated rat models of diabetic macroangiopathy induced by High fat of 16weeks. A total of 15 GK rats were constructed as a test group, along with 15 Wistar rats set as control group, and thoracic aorta tissue from each group was collected. Whole genomic RNA sequencing was performed on thoracic aorta tissue; 3223 novel lncRNAs and 20367 annotated lncRNAs were indemnified in thoracic aorta samples, and 864 lncRNAs were expressed differently in the test and control groups. Gene ontology term enrichment showed the apparent enrichment of inflammatory response and cell apoptosis, which consistent with the results of H&E Staining, TUNEL Assay, and ELISA; Extensive literature reveals inflammatory response and cell apoptosis play an important role in the process of diabetic macroangiopathy. The results of the present study indicated that lncRNAs, especially Nrep. bSep08, Col5a1, aSep0, soygee.aSep08-unspliced, NONRATT013247.2, votar.aSep08-unspliced, etc, both participate in and mediate the process of inflammatory response, cell apoptosis. What’s more. Our research provides further insights into understanding of the basic molecular mechanisms underlying diabetic macroangiopathy.

The role of the angiosomaly-oriented endovascular revascularization method in the complex treatment of diabetic foot syndrome

Objective: analyze the effectiveness of the angiosomal oriented endovascular revascularization method in the complex treatment of diabetic foot syndrome (DFS). Materials and methods. One of the most serious complications of diabetes mellitus is damage to the vessels of the lower extremities. In diabetic macroangiopathy, an extended lesion of medium-sized arteries occurs, which, coupled with an atherosclerotic lesion, often leads to the formation of arterial stenosis and occlusion. The leading method for correcting the patency of the great vessels today is endovascular balloon angioplasty. The study examined the feasibility of selective angiosomal revascularization of the lower extremities. The advantages of angiosomaly-oriented endovascular revascularization are a reduction in the duration of the intervention, a decrease in the volume of the injected contrast drug, and targeted restoration of blood flow in the arteries that feed the affected segment of the limb. The study included 49 patients with a neuroischemic form of DFS with hemodynamically significant stenosis and occlusion of the lower extremities arteries. Patients were divided into 2 groups. Patients of both groups underwent complex conservative treatment and performed operations on the lower extremities (from surgical debridement to below the knee amputation). Patients of the first group underwent angiosomaly oriented revascularization of the lower extremities. Patients from the second group underwent traditional endovascular revascularization. Results. After angiosomaly oriented revascularization, a complete restoration of the initial diameter of the vessel was achieved in 80.0 % of cases, the absence of residual stenosis – in 82.5 %, the absence of intimal dissection – in 95.0 % of cases. It was possible to achieve laminar blood flow in 90.0 % of cases. A reduction in the revascularization procedure by an average of 30 minutes and a decrease in the consumption of contrasting pharmaceuticals by an average of 100.0 ml are shown. Conclusion. When evaluating the results of complex treatment of patients after angiosomaly oriented revascularization, a decrease in the average hospital stay (11 and 13 days, respectively), a decrease in the average healing time of a wound defect by 1.25 times, a decrease in the average duration of ulcerative epithelization (9 and 13 days, respectively) and a decrease in the volume of surgical intervention and the number of high amputations during the year after angioplasty compared with patients who underwent endovascular revascularization according to the traditional method.

Combination of Astragalus membranaceous and Angelica sinensis Ameliorates Vascular Endothelial Cell Dysfunction by Inhibiting Oxidative Stress

Vascular endothelial dysfunction is an essential and early sign of diabetic macroangiopathy, a primary complication of diabetes mellitus. Astragalus membranaceous-Angelica sinensis is a classic medical combination applied in China to treat diabetes mellitus. The aim of this study was to investigate the effect of the granule form of the extract produced from the dried root of Astragalus membranaceous (AM) combination with the granule form of the extract produced from the dried Angelica sinensis (AS) on diabetic macroangiopathy and its underlying mechanism. Herein, rats were treated by AM-AS at a ratio of 3 : 2 via intragastric administration. High glucose-induced human umbilical vein vascular endothelial cells (HUVECs) were then treated with drug-containing serum collected from the rats. In high glucose-treated HUVECs, AM-AS combination increased cell viability (P<0.05), decreased the percentage of apoptotic cells (P<0.05) and the expression of the proapoptosis protein caspase 3 (P<0.05), reduced the proportion of cells in the G0/G1 phase (P<0.05), decreased reactive oxygen species level (P<0.05), enhanced cell migration and invasion (P<0.05), and reduced the level of 8-iso-prostaglandin F2alpha. These results indicate that AM-AS combination at the ratio of 3 : 2 ameliorated HUVEC dysfunction by regulating apoptosis, cell migration, and invasion, which might be mediated by their regulatory effect on reactive oxygen species production. The current study provides a theoretical basis for the treatment of diabetic macroangiopathy using AM-AS.