TY - JOUR
T1 - HDL stimulation of endothelial nitric oxide synthase
T2 - A novel mechanism of HDL action
AU - Mineo, Chieko
AU - Shaul, Philip W.
N1 - Funding Information:
This work was supported by Scientist Development Program (0235107N) from the American Heart Association (to C.M.) and NIH (Grants HL58888, HL53546, and HD30276 (to P.W.S.).
PY - 2003/8
Y1 - 2003/8
N2 - High-density lipoprotein (HDL), apolipoprotein A-I (apoA-I), and the principal high-affinity HDL receptor, scavenger receptor class B type I (SR-BI), are antiatherogenic and beneficial to the response to vascular injury. However, the fundamental mechanisms underlying these properties remain complex and not well understood. Recent work in both cell culture and in mice indicates that HDL causes robust activation of endothelial nitric oxide synthase (eNOS), and that this effect is mediated in endothelial cell caveolae by SR-BI through a process that requires apoA-I binding. Further studies have revealed that HDL stimulates eNOS through src- and PI3 kinase-mediated signaling, which leads to parallel activation of Akt and mitogen-activated protein kinases and their resultant independent modulation of the enzyme. As such, signaling initiated by HDL increases the production of the potent atheroprotective molecule nitric oxide, and this novel mechanism of action may be critically involved in the impact of the lipoprotein on vascular health and disease.
AB - High-density lipoprotein (HDL), apolipoprotein A-I (apoA-I), and the principal high-affinity HDL receptor, scavenger receptor class B type I (SR-BI), are antiatherogenic and beneficial to the response to vascular injury. However, the fundamental mechanisms underlying these properties remain complex and not well understood. Recent work in both cell culture and in mice indicates that HDL causes robust activation of endothelial nitric oxide synthase (eNOS), and that this effect is mediated in endothelial cell caveolae by SR-BI through a process that requires apoA-I binding. Further studies have revealed that HDL stimulates eNOS through src- and PI3 kinase-mediated signaling, which leads to parallel activation of Akt and mitogen-activated protein kinases and their resultant independent modulation of the enzyme. As such, signaling initiated by HDL increases the production of the potent atheroprotective molecule nitric oxide, and this novel mechanism of action may be critically involved in the impact of the lipoprotein on vascular health and disease.
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U2 - 10.1016/S1050-1738(03)00098-7
DO - 10.1016/S1050-1738(03)00098-7
M3 - Review article
C2 - 12922018
AN - SCOPUS:0041559836
SN - 1050-1738
VL - 13
SP - 226
EP - 231
JO - Trends in Cardiovascular Medicine
JF - Trends in Cardiovascular Medicine
IS - 6
ER -