Incorporation of nitric oxide-releasing crosslinked polyethyleneimine microspheres into vascular grafts

Pulfer, Sharon K.; Ott, Donald; Smith, Daniel J.

doi:10.1002/(sici)1097-4636(199711)37:2<182::aid-jbm6>3.0.co;2-n

Cited by 60 publications

(17 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Drug-eluting vascular stents with a variety of coatings (including fibrin, heparin, and multiple polymers) that contain NO donors have been tested with variable effects. 64,65 NO-containing cross-linked polyethylenimine microspheres that release 10 nmol NO/mg with a half-life of 51 hours have been applied to vascular grafts 66 to prevent thrombosis and restenosis. Similarly, the N(O)NO group has been incorporated into polymeric matrices synthesized to modulate the time course of NO release 67 ; this approach showed potent antiplatelet activity in a vascular graft in baboons.…”

Section: Delivery Systems and Drug Targetingmentioning

confidence: 99%

Nitric Oxide Donors and Cardiovascular Agents Modulating the Bioactivity of Nitric Oxide

Ignarro

Napoli

Loscalzo

2002

Circulation Research

444

335

View full text Add to dashboard Cite

Abstract-Nitric oxide (NO) mediates multiple physiological and pathophysiological processes in the cardiovascular system. Pharmacological compounds that release NO have been useful tools for evaluating the pivotal role of NO in cardiovascular physiology and therapeutics. These agents constitute two broad classes of compounds, those that release NO or one of its redox congeners spontaneously and those that require enzymatic metabolism to generate NO. In addition, several commonly used cardiovascular drugs exert their beneficial action, in part, by modulating the NO pathway. Here, we review these classes of agents, summarizing their fundamental chemistry and pharmacology, and provide an overview of their cardiovascular mechanisms of action. ysfunction of the normally protective endothelium is found in several cardiovascular diseases, including atherosclerosis, hypertension, heart failure, coronary heart disease, arterial thrombotic disorders, and stroke. [1][2][3][4][5][6] Endothelial dysfunction leads to nitric oxide (NO) deficiency, 1,6 -11 which has been implicated in the underlying pathobiology of many of these disorders (NO insufficiency states). (For a detailed overview of the role of NO in cardiovascular biology and pathobiology, the reader is referred to Loscalzo and Vita. 3 ) NO insufficiency may reflect an absolute deficit of NO (synthesis), impaired availability of bioactive NO, or enhanced NO inactivation. Whatever its biochemical basis, NO insufficiency limits NO-mediated signal transduction of normal or protective physiological processes. In light of this pathobiology, replacement or augmentation of endogenous NO by exogenously administered NO donors has provided the foundation for a broad field of pharmacotherapeutics in cardiovascular medicine.Organic nitrate and nitrite esters represent a time-honored class of NO-donating agents used in cardiovascular therapeutics since the 19th century. These agents have direct vasoactive effects that have been used to treat ischemic heart disease, heart failure, and hypertension for many years. Treatment with conventional nitrate preparations is limited by their therapeutic half-life, systemic absorption with potentially adverse hemodynamic effects, and drug tolerance. 1,6 To overcome these limitations, novel NO donors that offer selective effects, a prolonged half-life, and a reduced incidence of drug tolerance have been developed. NO donors are pharmacologically active substances that spontaneously release, or are metabolized to, NO or its redox congeners. In the present article, we review our current understanding of NO-donating compounds and of cardiovascular drugs that modulate the bioactivity of endogenously produced NO. NO DonorsBecause of the limited utility of authentic NO gas in many experimental systems and the short half-life of NO in vivo, compounds that have the capacity to release NO have been widely used as therapeutic agents and as pharmacological tools to investigate the role of NO in cardiovascular physiology and pathophysiology. Several NO do...

show abstract

Section: Delivery Systems and Drug Targetingmentioning

confidence: 99%

Nitric Oxide Donors and Cardiovascular Agents Modulating the Bioactivity of Nitric Oxide

Ignarro

Napoli

Loscalzo

2002

Circulation Research

444

335

View full text Add to dashboard Cite

show abstract

“…Recently, vascular grafts releasing NO infer possibilities preventing thrombosis and stenosis. 2,3 However, they are far from practical use, because the material requires more improvement.…”

mentioning

confidence: 99%

Synthetic Vascular Prosthesis Impregnated With Mesenchymal Stem Cells Overexpressing Endothelial Nitric Oxide Synthase

et al. 2006

View full text Add to dashboard Cite

Background-Endothelial dysfunction is known to exaggerate coronary artery disease, sometimes leading to irreversible myocardial damage. In such cases, repetitive coronary revascularization including coronary artery bypass grafting is needed, which may cause a shortage of graft conduits. On the other hand, endothelial nitric oxide synthase (eNOS) is an attractive target of cardiovascular gene therapy. The vascular prostheses, of which the inner surfaces are covered with mesenchymal stem cells (MSCs) overexpressing eNOS, are expected to offer feasible effects of NO and angiogenic effects of MSCs on the native coronary arterial beds, as well as improvement of self-patency. Herein, we attempted to develop small caliber vascular prostheses generating the bioactive proteins. Also, we attempted to transduce eNOS cDNA into MSCs. Methods and Results-The MSCs were isolated from rat bone marrow and transduced with each adenovirus harboring rat eNOS cDNA and ␤-galactosidase (␤-gal) (eNOS/MSCs and ␤-gal/MSCs). The ␤-gal/MSCs were impregnated into vascular prostheses, then the expressions of ␤-gal on the inner surfaces of them were evaluated by 5-bromo-4-chloro-3-indolyl ␤-D-galactoside staining. The NOS activity of eNOS/MSCs was assayed by monitoring the conversion of 3 H-arginine to 3 H-citrulline. The inner surfaces of the vascular prostheses were covered with MSCs expressing ␤-gal. The amount of the 3 H-citrulline increased, and eNOS/MSCs were determined to generate enzymatic activity of eNOS. This activity was completely inhibited by N G -nitro-L-arginine methyl ester. Key Words: mesenchymal stem cells Ⅲ endothelial nitric oxide synthase Ⅲ gene-transduction Ⅲ adenovirus Ⅲ small caliber expanded polytetrafluoroethylene (ePTFE) vascular prosthesis I mpaired endothelial function induces several cardiovascular diseases, including atherosclerosis, hypertension, heart failure, arteriosclerosis obliterans, and coronary heart disease. Endothelial dysfunction also causes NO insufficiency, resulting in the limitation of NO-mediated signal transduction and excretion of bioactive hormone-like products. 1 The attenuated production of NO and the hormone-like products exaggerates these cardiovascular diseases further. Coronary artery disease is one of the most critical diseases enhanced by endothelial dysfunction, sometimes leading to irreversible myocardial damage. Some patients require repetitive coronary revascularization, including coronary artery bypass grafting, which may lead to a shortage of graft materials. Conclusions-TheSmall caliber vascular prostheses, which would be suitable for graft conduits for coronary artery bypass grafting or arteriosclerosis obliterans below the knee, have an extremely high failure rate that is attributed to thrombus formation and occlusion. Many attempts have been made to increase the patency of small-caliber vascular prostheses over the years. Recently, vascular grafts releasing NO infer possibilities preventing thrombosis and stenosis. 2,3 However, they are far from practical use, because the ma...

show abstract

“…[54,55] Since then, current approaches in the development of NO-releasing and -generating polymers have shown some promise in vivo, but reduced clinical translation so far due to various limitations. For that reason, revolutionary strategies are necessary to advance the field into a more practical direction.…”

Section: Novel No-releasing and No-generating Polymeric Materialsmentioning

confidence: 99%

Polymer‐Based Nitric Oxide Therapies: Recent Insights for Biomedical Applications

Jen¹,

Serrano²,

Lith³

et al. 2011

Adv Funct Materials

164

152

View full text Add to dashboard Cite

Since the discovery of nitric oxide (NO) in the 1980s, this cellular messenger has been shown to participate in diverse biological processes such as cardiovascular homeostasis, immune response, wound healing, bone metabolism, and neurotransmission. Its beneficial effects have prompted increased research in the past two decades, with a focus on the development of materials that can locally release NO. However, significant limitations arise when applying these materials to biomedical applications. This Feature Article focuses on the development of NO-releasing and NO-generating polymeric materials (2006–2011) with emphasis on recent in vivo applications. Results are compared and discussed in terms of NO dose, release kinetics, and biological effects, in order to provide a foundation to design and evaluate new NO therapies.

show abstract

Incorporation of nitric oxide-releasing crosslinked polyethyleneimine microspheres into vascular grafts

Cited by 60 publications

References 39 publications

Nitric Oxide Donors and Cardiovascular Agents Modulating the Bioactivity of Nitric Oxide

Nitric Oxide Donors and Cardiovascular Agents Modulating the Bioactivity of Nitric Oxide

Synthetic Vascular Prosthesis Impregnated With Mesenchymal Stem Cells Overexpressing Endothelial Nitric Oxide Synthase

Polymer‐Based Nitric Oxide Therapies: Recent Insights for Biomedical Applications

Contact Info

Product

Resources

About