Cell lines

Mononuclear cells and VSMC

Preparation method

The solubility of this compound in DMSO is > 57.8 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months.

Reacting condition

0.1 or 1 μM

Applications

In mononuclear cells and VSMC, Atorvastatin Calcium (0.1 μM) significantly inhibited NF-κB activation induced by Ang II and TNF-α. Besides, Atorvastatin Calcium (1 μM) also down-regulated MCP-1 and IP-10 expressions induced by Ang II and by TNF-α.

Animal models

Ischemic hindlimb mice

Dosage form

2 or 8 mg/kg/day; p.o.; 4 weeks

Applications

In ischemic hindlimb mice, Atorvastatin Calcium at the dose of 8 mg/kg significantly recovered blood flow. Besides, the ischemia/normal perfusion ratio in the 8 mg/kg Atorvastatin Calcium treatment group also increased. According to the analyses of the ischemic muscle tissues, Atorvastatin Calcium significantly increased the number of capillaries. Meanwhile, CXCR4 expression was up-regulated in these ischemic tissues.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Atorvastatin Calcium is a potent inhibitor of HMG-CoA reductase with IC50 value of 150 nM[1].
HMG-CoA reductase is the key enzyme of the mevalonate pathway which produces cholesterol. HMG-CoA is the rate-limiting enzyme and is important for lowering the blood cholesterol levels. HMG-CoA reductase is located in the endoplasmic reticulum and contains eight transmembrane domains. The inhibitors of HMG-CoA reductase can induce the LDL (low density lipoprotein) receptors expression in the liver. It leads to increase the catabolism levels of plasma LDL and lower the concentration of plasma cholesterol which is an important determinant of atherosclerosis. HMG-CoA reductase plays an important role in cholesterol synthesis. HMG-CoA is the ony target for cholesterol-lowering drugs. HMG-CoA reductase is also an important enzyme for development. The activity of HMG-CoA reductase is related to germ cell migration defects. Inhibition of its activity can leadto intracerebral hemorrhage[1].
Atorvastatin is an HMG-CoA reductase inhibitor with IC50 value of 154 nM. It is effective in treating certain dyslipidemias and hypercholesterolemia[1]. Atorvastatin treatment at 40 mg decreases total cholesterol of 40% after 40 days.[1] It also be used to treat coronary or stroke patients with normal cholesterol levels.[2] Atorvastatin also decreases low density lipoprotein apheresis in patients by inducing LDL-receptors expression.
It is metabolized to several metabolites which are important for the effect of the therapeutic actions by CYP3A4 (cytochrome P450 3A4).[3]
References:
[1].    van Dam M, Zwart M, de Beer F, Smelt AH, Prins MH, Trip MD, Havekes LM, Lansberg PJ, Kastelein JJ: Long term efficacy and safety of atorvastatin in the treatment of severe type III and combined dyslipidaemia. Heart 2002, 88(3):234-238.
[2].    Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT et al: Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003, 361(9364):1149-1158.
[3].    Lennernas H: Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet 2003, 42(13):1141-1160.