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.
journal_name
Atherosclerosisjournal_title
Atherosclerosisauthors
Alfon J,Guasch JF,Berrozpe M,Badimon Ldoi
10.1016/s0021-9150(99)00084-2keywords:
subject
Has Abstractpub_date
1999-08-01 00:00:00pages
325-31issue
2eissn
0021-9150issn
1879-1484pii
S0021-9150(99)00084-2journal_volume
145pub_type
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