Latest research on LOVASTATIN

Lovastatin is a cholesterol-lowering agent that belongs to the class of medications called statins. It was the second agent of this class discovered. It was discovered by Alfred Alberts and his team at Merck in 1978 after screening only 18 compounds over 2 weeks. The agent, also known as mevinolin, was isolated from the fungi Aspergillus terreus. Research on this compound was suddenly shut down in 1980 and the drug was not approved until 1987. Interesting, Akira Endo at Sankyo Co. (Japan) patented lovastatin isolated from Monascus ruber four months before Merck. Lovastatin was found to be 2 times more potent than its predecessor, mevastatin, the first discovered statin. Like mevastatin, lovastatin is structurally similar to hydroxymethylglutarate (HMG), a substituent of HMG-Coenzyme A (HMG-CoA), a substrate of the cholesterol biosynthesis pathway via the mevalonic acid pathway. Lovastatin is a competitive inhibitor of HMG-CoA reductase with a binding affinity 20,000 times greater than HMG-CoA. Lovastatin differs structurally from mevastatin by a single methyl group at the 6’ position. Lovastatin is a prodrug that is activated by in vivo hydrolysis of the lactone ring. It, along with mevastatin, has served as one of the lead compounds for the development of the synthetic compounds used today.

Latest findings

We tested the possibility that cholesterol might indirectly regulate SMO activation by feedback inhibition of the synthesis of 7DHC, by blocking 7DHC synthesis with the HMGCR inhibitor LOVASTATIN. [source, 2016]
LOVASTATIN treatment did not have a positive effect on SHH signalling when DHCR7 activity was inhibited with BM15.766 (Fig. 5C), despite dramatically reducing the accumulation of 7DHC (Fig. 5D). [source, 2016]
We first demonstrated the activity of 7DHC by its ability to rescue the previously reported reduced SHH response in WT cells cultured in the presence of cyclodextrin and LOVASTATIN (Fig. 5F) (84). [source, 2016]
LOVASTATIN (Sigma) solubilized in H2O was present at a concentration of 5 μm in assays. [source, 2016]
Since statins exhibit pleotropic atheroprotective effects on endothelial cells38, we examined whether LOVASTATIN treatment of TEBVs could block the response to TNF-α. [source, 2016]
Endothelialized hNDF-TEBVs were matured for one week, and then exposed to 1 μM LOVASTATIN in the flow circuit for 3 days, or maintained without treatment, after which they were exposed to 200 U/mL TNF-α for 4.5 hours. [source, 2016]
Exposure to TNF-α or LOVASTATIN had no effect on the endothelium-independent response to Phenylephrine (Fig. 7a). [source, 2016]
While vessels not pre-treated with LOVASTATIN prior to exposure to TNF-α did not undergo vasodilation in response to acetylcholine, exposure to LOVASTATIN sustained vasodilation in response to acetylcholine after exposure to TNF-α on Day 10 (Fig. 7b). [source, 2016]
Lastly, we exposed the TEBVs to 1 μM LOVASTATIN for 3 days prior to exposure to TNF-α, and pretreatment of TEBVs with LOVASTATIN enabled them to Maintain endothelium-dependent vasodilation in response to acetylcholine after exposure to TNF-α, while untreated TEBVs experienced significantly reduced dilation. [source, 2016]
LOVASTATIN exhibits pleiotropic atheroprotective effects on endothelial cells by upregulating endothelial Nitric oxide synthase (eNOS) expression under inflammatory conditions50. [source, 2016]