OBJECTIVE: We tested for synergy between pravastatin and D-4F by administering oral doses of each in combination that were predetermined to be ineffective when given as single agents. METHODS AND RESULTS: The combination significantly increased high-density lipoprotein (HDL)-cholesterol levels, apolipoprotein (apo)A-I levels, paraoxonase activity, rendered HDL antiinflammatory, prevented lesion formation in young (79% reduction in en face lesion area; P<0.0001) and caused regression of established lesions in old apoE null mice (ie, mice receiving the combination for 6 months had lesion areas that were smaller than those before the start of treatment (P=0.019 for en face lesion area; P=0.004 for aortic root sinus lesion area). After 6 months of treatment with the combination, en face lesion area was 38% of that in mice maintained on chow alone; P<0.00004) with a 22% reduction in macrophage content in the remaining lesions (P=0.001), indicating an overall reduction in macrophages of 79%. The combination increased intestinal apoA-I synthesis by 60% (P=0.011). In monkeys, the combination also rendered HDL antiinflammatory. CONCLUSIONS: These results suggest that the combination of a statin and an HDL-based therapy may be a particularly potent treatment strategy.
OBJECTIVE: We tested for synergy between pravastatin and D-4F by administering oral doses of each in combination that were predetermined to be ineffective when given as single agents. METHODS AND RESULTS: The combination significantly increased high-density lipoprotein (HDL)-cholesterol levels, apolipoprotein (apo)A-I levels, paraoxonase activity, rendered HDL antiinflammatory, prevented lesion formation in young (79% reduction in en face lesion area; P<0.0001) and caused regression of established lesions in old apoE null mice (ie, mice receiving the combination for 6 months had lesion areas that were smaller than those before the start of treatment (P=0.019 for en face lesion area; P=0.004 for aortic root sinus lesion area). After 6 months of treatment with the combination, en face lesion area was 38% of that in mice maintained on chow alone; P<0.00004) with a 22% reduction in macrophage content in the remaining lesions (P=0.001), indicating an overall reduction in macrophages of 79%. The combination increased intestinal apoA-I synthesis by 60% (P=0.011). In monkeys, the combination also rendered HDL antiinflammatory. CONCLUSIONS: These results suggest that the combination of a statin and an HDL-based therapy may be a particularly potent treatment strategy.
Authors: Theodoros Kelesidis; Judith S Currier; Diana Huynh; David Meriwether; Christina Charles-Schoeman; Srinivasa T Reddy; Alan M Fogelman; Mohamad Navab; Otto O Yang Journal: J Lipid Res Date: 2011-09-27 Impact factor: 5.922
Authors: Wilissa D'Souza; John A Stonik; Andrew Murphy; Steven J Demosky; Amar A Sethi; Xiao L Moore; Jaye Chin-Dusting; Alan T Remaley; Dmitri Sviridov Journal: Circ Res Date: 2010-05-27 Impact factor: 17.367
Authors: K K Gkouskou; M Ioannou; G A Pavlopoulos; K Georgila; A Siganou; G Nikolaidis; D C Kanellis; S Moore; K A Papadakis; D Kardassis; I Iliopoulos; F A McDyer; E Drakos; A G Eliopoulos Journal: Oncogene Date: 2015-08-17 Impact factor: 9.867
Authors: Geoffrey D Wool; Veneracion G Cabana; John Lukens; Peter X Shaw; Christoph J Binder; Joseph L Witztum; Catherine A Reardon; Godfrey S Getz Journal: FASEB J Date: 2010-09-27 Impact factor: 5.191
Authors: Mohamad Navab; Ishaiahu Shechter; G M Anantharamaiah; Srinivasa T Reddy; Brian J Van Lenten; Alan M Fogelman Journal: Arterioscler Thromb Vasc Biol Date: 2009-07-16 Impact factor: 8.311