Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases.
Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases.
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DOI：
10.1038/s41598-017-08441-9
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发表时间：
2017-08-18
影响因子：
4.6
通讯作者：
Acharya S
中科院分区：
文献类型：
--
作者：
Le DQ;Kuriakose AE;Nguyen DX;Nguyen KT;Acharya S
一氧化氮(NO)通过增加血管内皮细胞(ECs)中的血管内皮生长因子(VEGF)水平，阻止血小板黏附和白细胞趋化，从而促进生理性血管生成，从而治疗外周动脉疾病(PAD)。然而，外周缺血期间持续的缺血事件会产生超氧化物，并通过形成有毒的过氧亚硝酸阴离子来降低NO的生物利用度。在这里，我们公开了一种有效的杂化分子4-(5-Amino-1，2，3-oxadiazol-3-yl)-2，2，6，6-tetramethyl-1-piperidinol(SA-2)，它同时包含抗氧化剂和NO供体功能，提供治疗水平的NO促进血管生成和保护内皮细胞免受过氧化氢诱导的氧化应激。化合物SA-2清除氧自由基，抑制血管内皮细胞(SMC)的增殖和迁移，促进内皮细胞形成管状结构。在体外基质细胞管形成实验中，与对照组相比，负载SA-2的共聚聚(乳酸-乙醇酸)(PLGA)纳米粒提供了持续数天的NO释放，改善了血清中水的稳定性，保护了内皮细胞免受氧化应激，并促进了应激条件下的血管生成。这些结果表明SA-2纳米粒有可能作为治疗PAD的替代疗法。
Nitric oxide (NO) has been known to promote physiological angiogenesis to treat peripheral arterial diseases (PAD) by increasing the vascular endothelial growth factor (VEGF) level in endothelial cells (ECs) and preventing platelet adherence and leukocyte chemotaxis. However, the ongoing ischemic event during peripheral ischemia produces superoxide and diminishes the NO bioavailability by forming toxic peroxynitrite anion. Here we disclose an efficacious hybrid molecule 4-(5-Amino-1,2,3-oxadiazol-3-yl)-2,2,6,6-tetramethyl-1-piperidinol (SA-2) containing both antioxidant and NO donor functionalities that provide a therapeutic level of NO necessary to promote angiogenesis and to protect ECs against hydrogen peroxide-induced oxidative stress. Compound SA-2 scavenged reactive oxygen species, inhibited proliferation and migration of smooth muscle cells (SMCs) and promoted the tube formation from ECs. Copolymer poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with SA-2 provided a sustained release of NO over days, improved aqueous stability in serum, protected ECs against oxidative stress, and enhanced angiogenesis under stress conditions as compared to that of the control in the in vitro matrigel tube formation assay. These results indicated the potential use of SA-2 nanoparticles as an alternative therapy to treat PAD.
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影响因子：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
3.7
作者：
Maruhashi T;Noma K;Iwamoto Y;Iwamoto A;Oda N;Kajikawa M;Matsumoto T;Hidaka T;Kihara Y;Chayama K;Nakashima A;Goto C;Liao JK;Higashi Y
通讯作者：
Higashi Y
影响因子：
2.9
作者：
Cianfarani, Francesca;Toietta, Gabriele;Odorisio, Teresa
通讯作者：
Odorisio, Teresa
影响因子：
3.9
作者：
Allen, Jason D.;Miller, Elizabeth M.;Annex, Brian H.
通讯作者：
Annex, Brian H.
影响因子：
3.1
作者：
Gkaliagkousi, Eugenia;Ferro, Albert
通讯作者：
Ferro, Albert