TY - JOUR
T1 - Adventitial contributions of the extracellular signal-regulated kinase and Akt pathways to neointimal hyperplasia
AU - Havelka, George E.
AU - Hogg, Melissa E.
AU - Martinez, Janet
AU - Banjeree, Monisha N.
AU - Jiang, Qun
AU - Kibbe, Melina R.
N1 - Funding Information:
Supported by the National Institutes of Health ( K08HL084203 to M.R.K., T32HL094293-01 to G.E.H.); Society for Vascular Surgery Foundation (M.R.K.); Institute for Women's Health Research, Northwestern University (M.R.K., M.E.H.); American Medical Association Foundation (M.E.H.); and a Northwestern University Undergraduate Research grant (M.N.B.).
PY - 2011/11
Y1 - 2011/11
N2 - Background: We recently reported that the efficacy of nitric oxide (NO) appears to be based on both sex and hormone status. The mechanism responsible for this differential efficacy is unknown. The aim of this study was to characterize the effect of sex, hormones, and NO on the extracellular signalregulated kinase (ERK) and Akt signaling pathways after arterial injury. Methods: Male and female SpragueDawley rats underwent castration or sham surgery. Two weeks later, they underwent carotid artery balloon injury. Treatment groups included the following: control, injury, and injury + 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) (n = 5 per group). Arteries were harvested 2 weeks after injury and assessed for phospho-ERK (pERK) and phospho-Akt (pAkt) expression. Results: After injury, more pERK and pAkt activity was seen in the adventitia than media in both sexes, regardless of hormone status (P <.05). In hormonally intact males, NO further increased pERK (44%) and pAkt (120%) after injury (P <.001). Castration attenuated the effects of NO. In hormonally intact females, NO caused the opposite pattern with pERK activity but did not affect pAkt activity. Conclusions: After arterial injury, ERK and Akt activity is significantly greater in the adventitia than the media, and depends on sex, hormone status, and NO. Understanding adventitial regulation of proliferative signaling pathways will allow the development of targeted therapies for neointimal hyperplasia.
AB - Background: We recently reported that the efficacy of nitric oxide (NO) appears to be based on both sex and hormone status. The mechanism responsible for this differential efficacy is unknown. The aim of this study was to characterize the effect of sex, hormones, and NO on the extracellular signalregulated kinase (ERK) and Akt signaling pathways after arterial injury. Methods: Male and female SpragueDawley rats underwent castration or sham surgery. Two weeks later, they underwent carotid artery balloon injury. Treatment groups included the following: control, injury, and injury + 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) (n = 5 per group). Arteries were harvested 2 weeks after injury and assessed for phospho-ERK (pERK) and phospho-Akt (pAkt) expression. Results: After injury, more pERK and pAkt activity was seen in the adventitia than media in both sexes, regardless of hormone status (P <.05). In hormonally intact males, NO further increased pERK (44%) and pAkt (120%) after injury (P <.001). Castration attenuated the effects of NO. In hormonally intact females, NO caused the opposite pattern with pERK activity but did not affect pAkt activity. Conclusions: After arterial injury, ERK and Akt activity is significantly greater in the adventitia than the media, and depends on sex, hormone status, and NO. Understanding adventitial regulation of proliferative signaling pathways will allow the development of targeted therapies for neointimal hyperplasia.
KW - Adventitia
KW - Akt
KW - ERK
KW - Neointimal hyperplasia
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U2 - 10.1016/j.amjsurg.2011.06.022
DO - 10.1016/j.amjsurg.2011.06.022
M3 - Article
C2 - 21906720
AN - SCOPUS:80054968484
VL - 202
SP - 515
EP - 519
JO - American Journal of Surgery
JF - American Journal of Surgery
SN - 0002-9610
IS - 5
ER -