Abstract 80: Modulating the Vascular Healing Response via SIRT1 Transgene Delivery

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Michele C Jen ◽  
Vincent Y Chen ◽  
Lonnie D Shea ◽  
Guillermo A Ameer

Bypass graft procedures are commonly performed to treat narrowing or blocked vessels. However, damage to the vascular wall from the surgical intervention can lead to pro-inflammatory events and oxidative stress that promote intimal hyperplasia and may eventually lead to restenosis. Therefore, strategies that seek to reduce inflammation and oxidative stress during the initial stages of wound healing at the graft anastomoses are expected to inhibit intimal hyperplasia and reduce graft failure rates. Sirtuin-1 (Sirt1), an NAD+-dependent lysine deacetylase, protects against inflammation and oxidative stress by deacetylating the RelA/p65 subunit of NF-kB and FOXO transcription factors. We hypothesize that the localized overexpression of Sirt1 at the perivascular wall via lentivirus entrapped in a thermoresponsive gel referred to as nanonets will lead to an improved vascular healing response at the graft anastomoses and attenuate intimal hyperplasia via reduced tissue inflammation and oxidative stress. Human aortic adventitial fibroblasts (AoAFs) were transduced with lentiviruses encoding for Sirt1 and assessed for NF-kB activity, cytokine expression, senescence, and upregulation of antioxidant genes. To assess perivascular transgene delivery, nanonets containing lentiviruses encoding GFP were applied perivascularly around the aortas of rats. After one week of in vivo transduction, aortas were explanted and probed for GFP positive cells. Upon TNFα stimulation, NF-kB activity and cytokine expression levels were decreased when compared to non-transduced and empty vector-transduced AoAFs. Furthermore, Sirt1-overexpression prevented cellular senescence and protected against oxidative stress. Nanonets containing lentiviruses effectively transduced adventitial fibroblasts in vivo. In conclusion, Sirt1 overexpression in AoAFs may be protective against inflammation and oxidative stress.

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Xiaozhong Huang ◽  
Yujuan Shi ◽  
Hongjin Chen ◽  
Rongrong Le ◽  
Xiaohua Gong ◽  
...  

AbstractDiabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.


2021 ◽  
Vol 186 ◽  
pp. 114490
Author(s):  
Karuppusamy Arunachalam ◽  
Amilcar Sabino Damazo ◽  
Antonio Macho ◽  
Monica Steffi Matchado ◽  
Eduarda Pavan ◽  
...  

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 507
Author(s):  
Rosaria Meccariello ◽  
Stefania D’Angelo

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.


2021 ◽  
Vol 96 ◽  
pp. 107593
Author(s):  
Yiming Ma ◽  
Lijuan Luo ◽  
Xiangming Liu ◽  
Herui Li ◽  
Zihang Zeng ◽  
...  

2019 ◽  
Vol 33 (1) ◽  
pp. 294-301
Author(s):  
Dessislava Lazarova ◽  
Sayaka Shibata ◽  
Itsuko Ishii ◽  
Genoveva Zlateva ◽  
Zhivko Zhelev ◽  
...  

2011 ◽  
Vol 74 (1) ◽  
pp. 150-156 ◽  
Author(s):  
Rizwan A. Ansari ◽  
Shakilur Rahman ◽  
Manpreet Kaur ◽  
Sameya Anjum ◽  
Sheikh Raisuddin

2021 ◽  
pp. 1-11
Author(s):  
Hanqing Chen ◽  
Xiru Xu ◽  
Zhengqing Liu ◽  
Yong Wu

Hypertension is considered a risk factor for a series of systematic diseases. Known factors including genetic predisposition, age, and diet habits are strongly associated with the initiation of hypertension. The current study aimed to investigate the role of miR-22-3p in hypertension. In this study, we discovered that the miR-22-3p level was significantly decreased in the thoracic aortic vascular tissues and aortic smooth muscle cells (ASMCs) of spontaneously hypertensive rats. Functionally, the overexpression of miR-22-3p facilitated the switch of ASMCs from the synthetic to contractile phenotype. To investigate the underlying mechanism, we predicted 11 potential target mRNAs for miR-22-3p. After screening, chromodomain helicase DNA-binding 9 (CHD9) was validated to bind with miR-22-3p. Rescue assays showed that the co-overexpression of miR-22-3p and CHD9 reversed the inhibitory effect of miR-22-3p mimics on cell proliferation, migration, and oxidative stress in ASMCs. Finally, miR-22-3p suppressed vascular remodeling and oxidative stress in vivo. Overall, miR-22-3p regulated ASMC phenotype switch by targeting CHD9. This new discovery provides a potential insight into hypertension treatment.


Author(s):  
Shreya Mandal ◽  
Arpita Patra ◽  
Shrabani Pradhan ◽  
Suchismita Roy ◽  
Animesh Samanta ◽  
...  

Objective: The aim of this study was to evaluate the antioxidant property of the isolated phytocompounds from TA (Terminalia arjuna) bark and in vivo study for nephro-protective and oxidative stress reducing activity in experimentally induced albino male rats.Methods: Fractions from methanol crude TA extract were collected by column chromatography and F27, F28, F29 fractions were selected on the basis of antioxidant property by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay. The in vivo study performed by 30 albino male rats which were randomly divided into five groups: Group I (control)were taken normal food and water, Groups II (uremic) were injected acetaminophen intraperitoneally at the dose of 500 mg/kg/d for 10 d, Group III, IV and V(extract treatment) acetaminophen intraperitoneally at the dose of 500 mg/kg/d for 10 d with co-administered orally of methanol fraction F27, F28, F29 at the dose of 100 mg/kg/d for 15 d respectively.Results: After scarification of rats, the uremic marker plasma urea (80%), creatinine (85%) were elevated and antioxidant enzyme marker such as plasma SOD and catalase level were significantly increased (p<0.05)in Group IV compared to Group II. The total phenolic content of the F28 methanolic fraction was (815.48±8.11) mg gallic acid equivalent/g of extract. For isolation of available compound by 1H NMR study in F28 methanol fraction of TA bark was arjunoside IV which contained olefinic proton (a pair of carbon atom linked with double bond).Conclusion: Among the three methanolic fraction of TA bark, F28 was shown best antioxidative, nephron-protective and oxidative stress reducing property. 


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