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Inhibition of LOX-1 by statins may relate to upregulation of eNOS.
Biochem Biophys Res Commun. 2001 Dec 14; 289(4):857-61.BB

Abstract

LOX-1, a receptor for oxidized low-density lipoprotein (ox-LDL), plays a critical role in endothelial dysfunction and atherosclerosis; both of these conditions are associated with diminished expression of constitutive endothelial nitric oxide synthase (eNOS). Recent studies show that HMG CoA reductase inhibitors (statins) exert cardioprotective effect. We examined the role of LOX-1 in eNOS expression and modulation of this relationship by two different statins, simvastatin and atorvastatin in human coronary artery endothelial cells (HCAECs). Ox-LDL (40 microg/ml) upregulated the expression of LOX-1; simultaneously, there was a reduction in eNOS expression. Pretreatment of HCAECs with simvastatin or atorvastatin (1 and 10 microM) reduced ox-LDL-induced upregulation of LOX-1 and downregulation of eNOS (both P < 0.05). High concentration of statins (10 microM) was more potent than the low concentration (1 microM) (P < 0.05). Both statins also attenuated ox-LDL-mediated activation of MAP kinase. These observations indicate that statins attenuate the effect of ox-LDL on eNOS expression. Inhibitory effect on LOX-1 and subsequently MAP kinase activity provides a potential mechanism of beneficial effects of statins beyond lowering cholesterol.

Authors+Show Affiliations

Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. mehtajl@uams.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

11735125

Citation

Mehta, J L., et al. "Inhibition of LOX-1 By Statins May Relate to Upregulation of ENOS." Biochemical and Biophysical Research Communications, vol. 289, no. 4, 2001, pp. 857-61.
Mehta JL, Li DY, Chen HJ, et al. Inhibition of LOX-1 by statins may relate to upregulation of eNOS. Biochem Biophys Res Commun. 2001;289(4):857-61.
Mehta, J. L., Li, D. Y., Chen, H. J., Joseph, J., & Romeo, F. (2001). Inhibition of LOX-1 by statins may relate to upregulation of eNOS. Biochemical and Biophysical Research Communications, 289(4), 857-61.
Mehta JL, et al. Inhibition of LOX-1 By Statins May Relate to Upregulation of ENOS. Biochem Biophys Res Commun. 2001 Dec 14;289(4):857-61. PubMed PMID: 11735125.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of LOX-1 by statins may relate to upregulation of eNOS. AU - Mehta,J L, AU - Li,D Y, AU - Chen,H J, AU - Joseph,J, AU - Romeo,F, PY - 2001/12/12/pubmed PY - 2002/2/22/medline PY - 2001/12/12/entrez SP - 857 EP - 61 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 289 IS - 4 N2 - LOX-1, a receptor for oxidized low-density lipoprotein (ox-LDL), plays a critical role in endothelial dysfunction and atherosclerosis; both of these conditions are associated with diminished expression of constitutive endothelial nitric oxide synthase (eNOS). Recent studies show that HMG CoA reductase inhibitors (statins) exert cardioprotective effect. We examined the role of LOX-1 in eNOS expression and modulation of this relationship by two different statins, simvastatin and atorvastatin in human coronary artery endothelial cells (HCAECs). Ox-LDL (40 microg/ml) upregulated the expression of LOX-1; simultaneously, there was a reduction in eNOS expression. Pretreatment of HCAECs with simvastatin or atorvastatin (1 and 10 microM) reduced ox-LDL-induced upregulation of LOX-1 and downregulation of eNOS (both P < 0.05). High concentration of statins (10 microM) was more potent than the low concentration (1 microM) (P < 0.05). Both statins also attenuated ox-LDL-mediated activation of MAP kinase. These observations indicate that statins attenuate the effect of ox-LDL on eNOS expression. Inhibitory effect on LOX-1 and subsequently MAP kinase activity provides a potential mechanism of beneficial effects of statins beyond lowering cholesterol. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/11735125/Inhibition_of_LOX_1_by_statins_may_relate_to_upregulation_of_eNOS_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(01)96070-X DB - PRIME DP - Unbound Medicine ER -