Lipophilic Statins May Treat Rheumatoid Arthritis

Researchers have found that lipophilic statins, drugs used to lower cholesterol levels, have potential for use in treating rheumatoid arthritis (RA) by inducing apoptosis in synovial cells.

Rheumatoid arthritis is characterized by synovial cell activation and proliferation. As statins are known to induce apoptosis in normal and tumor cells, investigators at Jichi Medical School (Tochigi, Japan) carried out a study to determine the effect of lipophilic and hydrophilic statins (fluvastatin and pravastatin, respectively) on apoptosis of cultures of synovial cells that had been taken from patients with RA or with osteoarthropathy.

They reported in the February 2006 issue of Arthritis & Rheumatism that fluvastatin, but not pravastatin, induced apoptosis in RA synovial cells in a concentration-dependent and time-dependent manner. Neither statin induced apoptosis in synovial cells from patients with osteoarthropathy.

On the molecular level, it was found that stimulation of apoptosis took place through a mitochondrial- and caspase 3-dependent pathway and by the blockage of mevalonate pathways, particularly through the inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathways.
These findings allowed the investigators to conclude, "The induction of apoptosis in RA synovial cells by fluvastatin and the biologic antiatherosclerotic properties of the statins suggest that they may turn out to be ideal therapeutic agents in RA. Based on these results, we propose that the statins warrant clinical trials as potential modifiers of RA.”



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Jichi Medical School