Br J Ophthalmol. 2005
Mar;89(3):275-9. The effects of atorvastatin in experimental
autoimmune uveitis.
Thomas PB, Albini T, Giri RK, See RF, Evans M, Rao NA.
Doheny Eye Institute, DVRC 211, 1450 San Pablo Street, Los Angeles
CA 90033, USA.
AIM: To investigate the effect of atorvastatin (Lipitor), a commonly
used drug for dyslipidaemia in experimental autoimmune uveitis (EAU).
METHODS: 48 B10-RIII mice were immunised with human interphotoreceptor
retinoid binding protein (IRBP) peptide p161-180. They were divided
into three groups of 16 each and treated orally once daily for 14
days; group one received phosphate buffered saline (control group),
group two received 1 mg/kg of atorvastatin (low dose group), and
group three received 10 mg/kg (high dose). On day 14 lymph nodes,
spleens, and right eyes were harvested. RNA was extracted from lymph
nodes for RNase protection assay (RPA) to determine proinflammatory
(IL-1alpha and IL-1beta), Th1 (TNF-alpha, IL-2, IL-12), and Th2
(IL-4, IL-5, and IL-10) cytokine levels. Protein was extracted from
spleens for western blot to detect the expression of phosphorylated
signal transducer and activator of transcription (STAT) 4 and STAT6.
The severity of inflammation in enucleated eyes was graded by a
masked observer. Paired t test was performed for the mean difference
in histological scoring between treated groups and the immunised
control group. RESULTS: Surprisingly, atorvastatin did not modulate
the immune response. The proinflammatory cytokines, IL-1alpha and
IL-1beta, and Th1 cytokines, TNF-alpha and IL-2, were upregulated
equally in control and atorvastatin treated groups. IL-12 and Th2
cytokines were not upregulated in all three groups. Western blot
analysis showed high levels of phosphorylated STAT4, but not STAT6
protein in the control and atorvastatin treated groups. Mean differences
in histological scoring between treated groups and the immunised
control group were not statistically significant. CONCLUSIONS: Atorvastatin
treatment had no effect on Th1 and Th2 cytokine transcription. Although
histological grading suggested mildly decreased inflammation in
the high dose treated group, the equivalence of cytokine expression
in all groups suggests that the statins may not modulate IRBP induced
uveoretinitis.
J Am Coll Cardiol. 2005 Mar 1;45(5):733-42.
Effect of lipid-lowering therapy
with atorvastatin on atherosclerotic aortic plaques detected by
noninvasive magnetic resonance imaging.
Yonemura A, Momiyama Y, Fayad ZA, Ayaori M, Ohmori R, Higashi
K, Kihara T, Sawada S, Iwamoto N, Ogura M, Taniguchi H, Kusuhara
M, Nagata M, Nakamura H, Tamai S, Ohsuzu F.
National Defense Medical College, Saitama, Japan.
OBJECTIVES: We sought to elucidate the effects of 20-mg versus
5-mg atorvastatin on thoracic and abdominal aortic plaques. BACKGROUND:
Regression of thoracic aortic plaques by simvastatin was demonstrated
using magnetic resonance imaging (MRI). However, the effects of
different doses of statin have not been assessed. METHODS: Using
MRI, we investigated the effects of 20-mg versus 5-mg atorvastatin
on thoracic and abdominal aortic plaques in 40 hypercholesterolemic
patients who were randomized to receive either dose. Treatment
effects were evaluated as changes in vessel wall thickness (VWT)
and vessel wall area (VWA) of atherosclerotic lesions from baseline
to 12 months of treatment. RESULTS: The 20-mg dose induced a greater
low-density lipoprotein (LDL) cholesterol reduction than did the
5-mg dose (-47% vs. -34%, p < 0.001). Although 20 mg and 5
mg reduced C-reactive protein (CRP) levels (-47% and -28%), the
degree of CRP reduction did not differ between the two doses.
The 20-mg dose reduced VWT and VWA of thoracic aortic plaques
(-12% and -18%, p < 0.001), whereas 5 mg did not (+1% and +4%).
Regarding abdominal aortic plaques, even 20 mg could not reduce
VWT or VWA (-1% and +3%), but instead progression was observed
with 5-mg treatment (+5% and +12%, p < 0.01). Notably, the
degree of plaque regression in thoracic aorta correlated with
LDL cholesterol (r = 0.64) and CRP (r = 0.49) reductions. Although
changes in abdominal aortic plaques only weakly correlated with
LDL cholesterol reduction (r = 0.34), they correlated with age
(r = 0.41). CONCLUSIONS: One-year 20-mg atorvastatin treatment
induced regression of thoracic aortic plaques with marked LDL
cholesterol reduction, whereas it resulted in only retardation
of plaque progression in abdominal aorta. Thoracic and abdominal
aortic plaques may have different susceptibilities to lipid lowering.
