UNASSIGNED: Statins lower plasma @entity165 by as much as 50%, thus reducing future cardiovascular events. However, the physiological effects of statins are diverse and not all are related to LDL-C lowering. We performed a small clinical pilot study to assess the impact of statins on lipoprotein-associated proteins in healthy individuals (n=10) with normal LDL-C (<130 mg/dL), who were treated with @entity8671 (20 mg/day) for 28 days. Proteomic analysis of size-exclusion chromatography isolated LDL, HDL-L (large) and HDL-S (small) fractions and spectral counting was used to compare relative protein detection before and after statin therapy. Significant protein changes were found in each lipoprotein pool and included both increases and decreases in several proteins involved in lipoprotein metabolism, complement regulation and acute phase response. The most dramatic effect of the @entity8671 treatment was an increase in @entity6417 ( @entity6417 ) spectral counts associated with HDL-L particles. Quantitative measurement by ELISA confirmed an average 5.7-fold increase in HDL-L associated @entity6417 . Molecular modeling predictions indicated that the hydrophobic reactive center loop of @entity6417 , the functional domain responsible for its protease inhibitor activity, is likely involved in its lipid binding and its association with HDL was found to protect @entity6417 against oxidative inactivation. Cell culture experiments, using J774 macrophages, demonstrated that the association of @entity6417 with HDL enhances its anti-protease activity, preventing elastase induced production of @entity5 necrosis factor alpha. In conclusion, we show that statins can significantly alter the protein composition of both LDL and HDL and our studies reveal a novel functional relationship between @entity6417 and HDL. The upregulation of @entity6417 on HDL enhances its anti-inflammatory functionality, which may contribute to the non-lipid lowering beneficial effects of statins.

XXXX Alters the Proteome of High Density Lipoproteins: Generation of Alpha-1-antitrypsin Enriched Particles with Anti-inflammatory Properties.

@entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity6417 :: ('5265', 'Gene') :: ['alpha-1-antirypsin', 'A1AT'] @entity8671 :: ('MESH:C422923', 'Chemical') :: ['rosuvastatin'] @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol']
@entity8671 :: (MESH:C422923,Chemical) :: ['Rosuvastatin']
