Dysfunction of endothelial nitric oxide synthase and atherosclerosis
- PMID: 15001455
- DOI: 10.1161/01.ATV.0000125114.88079.96
Dysfunction of endothelial nitric oxide synthase and atherosclerosis
Abstract
Atherosclerosis is associated with an impairment of endothelium-dependent relaxations, which represents the reduced bioavailability of nitric oxide (NO) produced from endothelial NO synthase (eNOS). Among various mechanisms implicated in the impaired EDR in atherosclerosis, superoxide generated from dysfunctional eNOS has attracted attention. Under conditions in which vascular tissue levels of tetrahydrobiopterin (BH4), a cofactor for NOS, are deficient or lacking, eNOS becomes dysfunctional and produces superoxide rather than NO. Experimental studies in vitro have revealed that NO from eNOS constitutes an anti-atherogenic molecule. A deficiency of eNOS was demonstrated to accelerate atherosclerotic lesion formation in eNOS knockout mice. In contrast, eNOS overexpression with hypercholesterolemia may promote atherogenesis via increased superoxide generation from dysfunctional eNOS. Thus, eNOS may have 2 faces in the pathophysiology of atherosclerosis depending on tissue BH4 metabolisms. An improved understanding of tissue BH4 metabolisms in atherosclerotic vessels is needed, which would help in developing new strategies for the inhibition and treatment of atherosclerosis.
Similar articles
-
The two faces of endothelial nitric oxide synthase in the pathophysiology of atherosclerosis.Endothelium. 2004 Mar-Apr;11(2):99-107. doi: 10.1080/10623320490482637. Endothelium. 2004. PMID: 15370069 Review.
-
Increased endothelial tetrahydrobiopterin synthesis by targeted transgenic GTP-cyclohydrolase I overexpression reduces endothelial dysfunction and atherosclerosis in ApoE-knockout mice.Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):445-50. doi: 10.1161/01.ATV.0000115637.48689.77. Epub 2004 Jan 5. Arterioscler Thromb Vasc Biol. 2004. PMID: 14707037
-
Malfunction of vascular control in lifestyle-related diseases: endothelial nitric oxide (NO) synthase/NO system in atherosclerosis.J Pharmacol Sci. 2004 Dec;96(4):411-9. doi: 10.1254/jphs.fmj04006x6. J Pharmacol Sci. 2004. PMID: 15613778 Review.
-
Augmented BH4 by gene transfer restores nitric oxide synthase function in hyperglycemic human endothelial cells.Cardiovasc Res. 2005 Mar 1;65(4):823-31. doi: 10.1016/j.cardiores.2004.10.040. Cardiovasc Res. 2005. PMID: 15721862
-
Nitric oxide dynamics and endothelial dysfunction in type II model of genetic diabetes.Eur J Pharmacol. 2005 Mar 21;511(1):53-64. doi: 10.1016/j.ejphar.2005.01.014. Eur J Pharmacol. 2005. PMID: 15777779
Cited by
-
Carbamylated erythropoietin-FC fusion protein and recombinant human erythropoietin during porcine kidney ischemia/reperfusion injury.Intensive Care Med. 2013 Mar;39(3):497-510. doi: 10.1007/s00134-012-2766-y. Epub 2013 Jan 5. Intensive Care Med. 2013. PMID: 23291730
-
Individual Responses to Heat Stress: Implications for Hyperthermia and Physical Work Capacity.Front Physiol. 2020 Sep 11;11:541483. doi: 10.3389/fphys.2020.541483. eCollection 2020. Front Physiol. 2020. PMID: 33013476 Free PMC article. Review.
-
Impaired vasodilation in the pathogenesis of hypertension: focus on nitric oxide, endothelial-derived hyperpolarizing factors, and prostaglandins.J Clin Hypertens (Greenwich). 2012 Apr;14(4):198-205. doi: 10.1111/j.1751-7176.2012.00606.x. J Clin Hypertens (Greenwich). 2012. PMID: 22458740 Free PMC article. Review.
-
Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies.Cardiovasc Diabetol. 2018 Aug 31;17(1):121. doi: 10.1186/s12933-018-0763-3. Cardiovasc Diabetol. 2018. PMID: 30170601 Free PMC article. Review.
-
Endothelial dysfunction in the streptozotocin-induced diabetic apoE-deficient mouse.Br J Pharmacol. 2005 Dec;146(8):1110-8. doi: 10.1038/sj.bjp.0706417. Br J Pharmacol. 2005. PMID: 16231005 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
