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Rac1 pharmacological inhibition rescues human endothelial dysfunction
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نویسنده
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carrizzo a. ,vecchione c. ,damato a. ,di nonno f. ,ambrosio m. ,pompeo f. ,cappello e. ,capocci l. ,peruzzi m. ,valenti v. ,biondi-zoccai g. ,m. marullo a.g. ,palmerio s. ,carnevale r. ,spinelli c.c. ,puca a.a. ,rubattu s. ,volpe m. ,sadoshima j. ,frati g. ,sciarretta s.
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منبع
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journal of the american heart association - 2017 - دوره : 6 - شماره : 3
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چکیده
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Background-endothelial dysfunction contributes significantly to the development of vascular diseases. however,a therapy able to reduce this derangement still needs to be identified. we evaluated the effects of pharmacological inhibition of rac1,a small gtpase protein promoting oxidative stress,in human endothelial dysfunction. methods and results-we performed vascular reactivity studies to test the effects of nsc23766,a rac1 inhibitor,on endothelium-dependent vasorelaxation of saphenous vein segments collected from 85 subjects who had undergone surgery for venous insufficiency and from 11 patients who had undergone peripheral vascular surgery. the endothelium-dependent vasorelaxation of the varicose segments of saphenous veins collected from patients with venous insufficiency was markedly impaired and was also significantly lower than that observed in control nonvaricose vein tracts from the same veins. rac1 activity,reactive oxygen species levels,and reduced nicotine adenine dinucleotide phosphate (nadph) oxidase activity were significantly increased in varicose veins,and nsc23766 was able to significantly improve endothelium-dependent vasorelaxation of dysfunctional saphenous vein portions in a nitric oxide-dependent manner. these effects were paralleled by a significant reduction of nadph oxidase activity and activation of endothelial nitric oxide synthase. finally,we further corroborated this data by demonstrating that rac1 inhibition significantly improves venous endothelial function and reduces nadph oxidase activity in saphenous vein grafts harvested from patients with vascular diseases undergoing peripheral bypass surgery. conclusions-rac1 pharmacological inhibition rescues endothelial function and reduces oxidative stress in dysfunctional veins. rac1 inhibition may represent a potential therapeutic intervention to reduce human endothelial dysfunction and subsequently vascular diseases in various clinical settings. © 2017 the authors.
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کلیدواژه
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Cardiovascular disease; Endothelial dysfunction; Nitric oxide; Oxidative stress
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آدرس
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irccs neuromed,pozzilli (is), Italy, irccs neuromed,pozzilli (is),italy,department of medicine and surgery,university of salerno,baronissi (sa), Italy, irccs neuromed,pozzilli (is), Italy, irccs neuromed,pozzilli (is), Italy, irccs neuromed,pozzilli (is), Italy, irccs neuromed,pozzilli (is), Italy, irccs neuromed,pozzilli (is), Italy, irccs neuromed,pozzilli (is), Italy, department of medical-surgical sciences and biotechnologies,sapienza university of rome polo pontino,latina, Italy, department of imaging,bambino gesù children hospital,irccs,rome, Italy, irccs neuromed,pozzilli (is),italy,department of medical-surgical sciences and biotechnologies,sapienza university of rome polo pontino,latina, Italy, department of medical-surgical sciences and biotechnologies,sapienza university of rome polo pontino,latina, Italy, department of medical-surgical sciences and biotechnologies,sapienza university of rome polo pontino,latina, Italy, department of medical-surgical sciences and biotechnologies,sapienza university of rome polo pontino,latina, Italy, irccs multimedica s.p.a,milan, Italy, department of medicine and surgery,university of salerno,baronissi (sa),italy,irccs multimedica s.p.a,milan, Italy, irccs neuromed,pozzilli (is),italy,department of clinical and molecular medicine,sapienza university of rome, Italy, irccs neuromed,pozzilli (is),italy,department of clinical and molecular medicine,sapienza university of rome, Italy, department of cell biology and molecular medicine,rutgers new jersey medical school,newark,nj, United States, irccs neuromed,pozzilli (is),italy,department of medical-surgical sciences and biotechnologies,sapienza university of rome polo pontino,latina, Italy, irccs neuromed,pozzilli (is),italy,department of medical-surgical sciences and biotechnologies,sapienza university of rome polo pontino,latina, Italy
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Authors
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