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Nitric oxide synthase II (NOS II) gene expression correlates with atherosclerotic intimal thickening. Preventive effects of HMG-CoA reductase inhibitors.
Atherosclerosis. 1999 Aug; 145(2):325-31.A

Abstract

HMG-CoA reductase inhibitors have been shown to be effective in primary and secondary prevention of coronary heart disease. Their mechanism of action is attributed to their cholesterol lowering activity but recent results seem to indicate additional effects related to the modulation of other processes that regulate the presentation of vascular diseases. Our objective has been to study the effects of atorvastatin and simvastatin, two HMG-CoA reductase inhibitors, on lesion composition and expression of genes involved in lesion development in a diet-induced atherosclerotic rabbit model. Both HMG-CoA reductase inhibitors were administered at identical doses of 2.5 mg/kg per day with the hyperlipemic diet for 10 weeks. Both statins significantly prevented the diet-induced increase in cholesterol levels. Relative lesion composition in fibrinogen, macrophages and smooth muscle cells was unaltered by the treatment although lesion size was reduced; therefore, both HMG-CoA reductase inhibitors reduced total amounts of fibrinogen, macrophages and smooth muscle cells (simvastatin, P < 0.05). NOS II gene expression was positively and significantly correlated with lesion size and inversely correlated with HDL plasma levels. NOS II expression was markedly downregulated in simvastatin treated animals while MCP-1 was unaltered. Therefore, HMG-CoA reductase inhibition seems to interfere with atherosclerotic lesion development by reducing intimal thickening development and the expression of the cytotoxic NOS II.

Authors+Show Affiliations

Cardiovascular Research Center, CSIC-HSCSP-UAB, Barcelona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10488960

Citation

Alfon, J, et al. "Nitric Oxide Synthase II (NOS II) Gene Expression Correlates With Atherosclerotic Intimal Thickening. Preventive Effects of HMG-CoA Reductase Inhibitors." Atherosclerosis, vol. 145, no. 2, 1999, pp. 325-31.
Alfon J, Guasch JF, Berrozpe M, et al. Nitric oxide synthase II (NOS II) gene expression correlates with atherosclerotic intimal thickening. Preventive effects of HMG-CoA reductase inhibitors. Atherosclerosis. 1999;145(2):325-31.
Alfon, J., Guasch, J. F., Berrozpe, M., & Badimon, L. (1999). Nitric oxide synthase II (NOS II) gene expression correlates with atherosclerotic intimal thickening. Preventive effects of HMG-CoA reductase inhibitors. Atherosclerosis, 145(2), 325-31.
Alfon J, et al. Nitric Oxide Synthase II (NOS II) Gene Expression Correlates With Atherosclerotic Intimal Thickening. Preventive Effects of HMG-CoA Reductase Inhibitors. Atherosclerosis. 1999;145(2):325-31. PubMed PMID: 10488960.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nitric oxide synthase II (NOS II) gene expression correlates with atherosclerotic intimal thickening. Preventive effects of HMG-CoA reductase inhibitors. AU - Alfon,J, AU - Guasch,J F, AU - Berrozpe,M, AU - Badimon,L, PY - 1999/9/17/pubmed PY - 1999/9/17/medline PY - 1999/9/17/entrez SP - 325 EP - 31 JF - Atherosclerosis JO - Atherosclerosis VL - 145 IS - 2 N2 - HMG-CoA reductase inhibitors have been shown to be effective in primary and secondary prevention of coronary heart disease. Their mechanism of action is attributed to their cholesterol lowering activity but recent results seem to indicate additional effects related to the modulation of other processes that regulate the presentation of vascular diseases. Our objective has been to study the effects of atorvastatin and simvastatin, two HMG-CoA reductase inhibitors, on lesion composition and expression of genes involved in lesion development in a diet-induced atherosclerotic rabbit model. Both HMG-CoA reductase inhibitors were administered at identical doses of 2.5 mg/kg per day with the hyperlipemic diet for 10 weeks. Both statins significantly prevented the diet-induced increase in cholesterol levels. Relative lesion composition in fibrinogen, macrophages and smooth muscle cells was unaltered by the treatment although lesion size was reduced; therefore, both HMG-CoA reductase inhibitors reduced total amounts of fibrinogen, macrophages and smooth muscle cells (simvastatin, P < 0.05). NOS II gene expression was positively and significantly correlated with lesion size and inversely correlated with HDL plasma levels. NOS II expression was markedly downregulated in simvastatin treated animals while MCP-1 was unaltered. Therefore, HMG-CoA reductase inhibition seems to interfere with atherosclerotic lesion development by reducing intimal thickening development and the expression of the cytotoxic NOS II. SN - 0021-9150 UR - https://www.unboundmedicine.com/medline/citation/10488960/Nitric_oxide_synthase_II__NOS_II__gene_expression_correlates_with_atherosclerotic_intimal_thickening__Preventive_effects_of_HMG_CoA_reductase_inhibitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(99)00084-2 DB - PRIME DP - Unbound Medicine ER -