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Aortic vascular smooth muscle cells (VSMC) were harvested from rodent models of type II DM (Zucker diabetic fatty), metabolic syndrome (obese Zucker), and their genetic control (lean Zucker). Interestingly, NO inhibited proliferation and induced G<jats:sub>0<\/jats:sub>\/G<jats:sub>1<\/jats:sub> cell cycle arrest to the greatest extent in VSMC from rodent models of metabolic syndrome and type II DM compared with controls. This heightened efficacy was associated with increased expression of cyclin-dependent kinase inhibitor p21, but not p27. Using the rat carotid artery injury model to assess the efficacy of NO in vivo, we found that the NO donor PROLI\/NO inhibited neointimal hyperplasia to the greatest extent in type II DM rodents, followed by metabolic syndrome, then controls. Increased neointimal hyperplasia correlated with increased reactive oxygen species (ROS) production, as demonstrated by dihydroethidium staining, and NO inhibited this increase most in metabolic syndrome and DM. In conclusion, NO was surprisingly a more effective inhibitor of neointimal hyperplasia following arterial injury in type II DM and metabolic syndrome vs. control. This heightened efficacy may be secondary to greater inhibition of VSMC proliferation through cell cycle arrest and regulation of ROS expression, in addition to other possible unidentified mechanisms that deserve further exploration. <\/jats:p>","DOI":"10.1152\/ajpheart.00185.2008","type":"journal-article","created":{"date-parts":[[2008,10,17]],"date-time":"2008-10-17T20:45:41Z","timestamp":1224276341000},"page":"H2388-H2398","source":"Crossref","is-referenced-by-count":27,"title":["Heightened efficacy of nitric oxide-based therapies in type II diabetes mellitus and metabolic syndrome"],"prefix":"10.1152","volume":"295","author":[{"given":"Sadaf S.","family":"Ahanchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinit N.","family":"Varu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nick D.","family":"Tsihlis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles G.","family":"Pearce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muneera R.","family":"Kapadia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qun","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph E.","family":"Saavedra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry K.","family":"Keefer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph A.","family":"Hrabie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melina R.","family":"Kibbe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1053\/ejvs.1999.0852"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000110785.96039.f6"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00982.2004"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.19.2570"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.63.070194.001135"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.6.1615"},{"key":"R7","unstructured":"Busija DW, Miller AW, Katakam P, Simandle S, Erdos B. 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