Nitric oxide releasing nanomatrix gel treatment inhibits venous intimal hyperplasia and improves vascular remodeling in a rodent arteriovenous fistula

Somarathna, Maheshika; Hwang, Patrick T.J.; Millican, R. Carl; Alexander, Grant C. B.; Isayeva-Waldrop, Tatyana; Sherwood, Jennifer; Brott, Brigitta C.; Falzon, Isabelle; Northrup, Hannah; Shiu, Yan-Ting; Stubben, Chris; Totenhagen, John; Jun, Ho−Wook; Lee, Timmy

doi:10.1016/j.biomaterials.2021.121254

Cited by 25 publications

(16 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…eNOS is upregulated in the venous limb following AVF creation, implicating NO in vascular adaptation to AVF creation [ 19 ]. Mouse AVF models have also suggested the importance of eNOS and NO in successful AVF maturation, with recent studies demonstrating that overexpression of eNOS results in favorable vascular profiles for AVF maturation, such as increased vein diameter and reduced NIH after AVF creation [ 20 , 21 , 22 ].…”

Section: Pathophysiology Of Venous Neointimal Hyperplasiamentioning

confidence: 99%

Localized Perivascular Therapeutic Approaches to Inhibit Venous Neointimal Hyperplasia in Arteriovenous Fistula Access for Hemodialysis Use

et al. 2022

View full text Add to dashboard Cite

An arteriovenous fistula (AVF) is the preferred vascular access for chronic hemodialysis, but high failure rates restrict its use. Optimizing patients’ perioperative status and the surgical technique, among other methods for preventing primary AVF failure, continue to fall short in lowering failure rates in clinical practice. One of the predominant causes of AVF failure is neointimal hyperplasia (NIH), a process that results from the synergistic effects of inflammation, hypoxia, and hemodynamic shear stress on vascular tissue. Although several systemic therapies have aimed at suppressing NIH, none has shown a clear benefit towards this goal. Localized therapeutic approaches may improve rates of AVF maturation by providing direct structural and functional support to the maturating fistula, as well as by delivering higher doses of pharmacologic agents while avoiding the adverse effects associated with systemic administration of therapeutic agents. Novel materials—such as polymeric scaffolds and nanoparticles—have enabled the development of different perivascular therapies, such as supportive mechanical devices, targeted drug delivery, and cell-based therapeutics. In this review, we summarize various perivascular therapeutic approaches, available data on their effectiveness, and the outlook for localized therapies targeting NIH in the setting of AVF for hemodialysis use. Highlights: Most systemic therapies do not improve AVF patency outcomes; therefore, localized therapeutic approaches may be beneficial. Locally delivered drugs and medical devices may improve AVF patency outcomes by providing biological and mechanical support. Cell-based therapies have shown promise in suppressing NIH by delivering a more extensive array of bioactive substances in response to the biochemical changes in the AVF microenvironment.

show abstract

Section: Pathophysiology Of Venous Neointimal Hyperplasiamentioning

confidence: 99%

Localized Perivascular Therapeutic Approaches to Inhibit Venous Neointimal Hyperplasia in Arteriovenous Fistula Access for Hemodialysis Use

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Although the PANO gel releases NO for up to a month, we applied the PANO gel biweekly. The tissue level of NO released from the PANO gel may be determined by multiple factors, including the injection volume and frequency, injection tissue, and body weight.…”

Section: Discussionmentioning

confidence: 99%

“…70 At present, it is unknown whether our observed effects of the PANO gel on cerebrovascular blood flow and cognitive function are the direct effect of NO or are mediated by the neuroprotective effects of the adipocyte beiging. 70 Although the PANO gel releases NO for up to a month, 24 we applied the PANO gel biweekly. The tissue level of NO released from the PANO gel may be determined by multiple factors, including the injection volume and frequency, injection tissue, and body weight.…”

Section: ■ Discussionmentioning

confidence: 99%

“…We have developed a peptide amphiphile (PA) nanomatrix gel that releases sustained levels of NO (PANO gel) for a month, and we previously demonstrated that the PANO gel enhances angiogenesis and suppresses inflammatory responses. − The nanomatrix gel is composed of PAs, comprising multilayers of hydrophilic NO-releasing peptide sequences conjugated to hydrophobic alkyl tails. This amphiphilic property of PAs promotes the self-assembly of PAs into cylindrical micelle nanofibers that form a nanomatrix gel through cross-linking by the addition of calcium ions. , The unique multilayered cylindrical micelle nanofibers with the NO-releasing peptide enable generating NO. − The goal of the present study is to evaluate the effects of exogenous NO by the PANO gel on BAT on subsequent beneficial effects, such as weight loss, insulin sensitivity, and cognitive function.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Subcutaneous Administration of a Nitric Oxide-Releasing Nanomatrix Gel Ameliorates Obesity and Insulin Resistance in High-Fat Diet-Induced Obese Mice

Ren

Hwang

Millican

et al. 2022

ACS Appl. Mater. Interfaces

Self Cite

View full text Add to dashboard Cite

Nitric oxide (NO) is a gaseous signaling molecule, which plays crucial roles in various biological processes, including inflammatory responses, metabolism, cardiovascular functions, and cognitive function. NO bioavailability is reduced with aging and cardiometabolic disorders in humans and rodents. NO stimulates the metabolic rate by increasing the mitochondrial biogenesis and brown fat activation. Therefore, we propose a novel technology of providing exogenous NO to improve the metabolic rate and cognitive function by promoting the development of brown adipose tissue. In the present study, we demonstrate the effects of the peptide amphiphiles–NO-releasing nanomatrix gel (PANO gel) on high-fat diet-induced obesity, insulin resistance, and cognitive functions. Eight-week-old male C57BL/6 mice were subcutaneously injected in the brown fat area with the PANO gel or vehicle (PA gel) every 2 weeks for 12 weeks. The PANO gel-injected mice gained less body weight, improved glucose tolerance, and decreased fasting serum insulin and leptin levels compared with the PA gel-injected mice. Insulin signaling in the muscle, liver, and epididymal white adipose tissue was improved by the PANO gel injection. The PANO gel reduced inflammation, increased lipolysis in the epididymal white adipose tissue, and decreased serum lipids and liver triglycerides. Interestingly, the PANO gel stimulated uncoupled protein 1 gene expression in the brown and beige fat tissues. Furthermore, the PANO gel increased the cerebral blood flow and improved learning and memory abilities. Our results suggest that using the PANO gel to supply exogenous NO is a novel technology to treat metabolic disorders and cognitive dysfunctions.

show abstract

“…It facilitates vascular homeostasis by maintaining vascular integrity and inhibiting platelet aggregation and neutrophil adhesion [ 75 , 76 ]. Nitric oxide also prevents the proliferation of artery smooth muscle cells in defense against atherosclerosis and neointima hyperplasia formation [ 77 , 78 ]. In addition, an increase in oxidative stress causes superoxide anion to degrade NO and form peroxynitrite ONOO− [ 79 ] which decreases the bioavailability of NO while triggering endothelial impairment [ 73 ].…”

Section: Hydroxytyrosol In Oxidative Stress-induced Endothelial Dysfu...mentioning

confidence: 99%

Effects of Hydroxytyrosol in Endothelial Functioning: A Comprehensive Review

et al. 2023

View full text Add to dashboard Cite

Pharmacologists have been emphasizing and applying plant and herbal-based treatments in vascular diseases for decades now. Olives, for example, are a traditional symbol of the Mediterranean diet. Hydroxytyrosol is an olive-derived compound known for its antioxidant and cardioprotective effects. Acknowledging the merit of antioxidants in maintaining endothelial function warrants the application of hydroxytyrosol in endothelial dysfunction salvage and recovery. Endothelial dysfunction (ED) is an impairment of endothelial cells that adversely affects vascular homeostasis. Disturbance in endothelial functioning is a known precursor for atherosclerosis and, subsequently, coronary and peripheral artery disease. However, the effects of hydroxytyrosol on endothelial functioning were not extensively studied, limiting its value either as a nutraceutical supplement or in clinical trials. The action of hydroxytyrosol in endothelial functioning at a cellular and molecular level is gathered and summarized in this review. The favorable effects of hydroxytyrosol in the improvement of endothelial functioning from in vitro and in vivo studies were scrutinized. We conclude that hydroxytyrosol is capable to counteract oxidative stress, inflammation, vascular aging, and arterial stiffness; thus, it is beneficial to preserve endothelial function both in vitro and in vivo. Although not specifically for endothelial dysfunction, hydroxytyrosol safety and efficacy had been demonstrated via in vivo and clinical trials for cardiovascular-related studies.

show abstract

Nitric oxide releasing nanomatrix gel treatment inhibits venous intimal hyperplasia and improves vascular remodeling in a rodent arteriovenous fistula

Cited by 25 publications

References 91 publications

Localized Perivascular Therapeutic Approaches to Inhibit Venous Neointimal Hyperplasia in Arteriovenous Fistula Access for Hemodialysis Use

Localized Perivascular Therapeutic Approaches to Inhibit Venous Neointimal Hyperplasia in Arteriovenous Fistula Access for Hemodialysis Use

Subcutaneous Administration of a Nitric Oxide-Releasing Nanomatrix Gel Ameliorates Obesity and Insulin Resistance in High-Fat Diet-Induced Obese Mice

Effects of Hydroxytyrosol in Endothelial Functioning: A Comprehensive Review

Contact Info

Product

Resources

About