Disruption of the murine procollagen C-proteinase enhancer 2 gene causes accumulation of pro-apoA-I and increased HDL levelsOmar L Francone
Department of Cardiovascular and Metabolic Diseases, Global Research and Development, Pfizer, Inc, Groton, CT, USA
J Lipid Res 52:1974-83. 2011
..ABCA1-dependent cholesterol efflux is defective in PCPE2 KO mice, suggesting that the functionality of HDL is altered...
Abnormal phospholipid composition impairs HDL biogenesis and maturation in mice lacking Abca1Omar L Francone
Pfizer Global Research and Development, Groton, Connecticut 06340, USA
Biochemistry 42:8569-78. 2003
..Taken together, these observations suggest that ABCA1 is necessary for the adequate lipidation of apoAI, which enables the interaction with LCAT and subsequent maturation...
- Increased cholesterol deposition, expression of scavenger receptors, and response to chemotactic factors in Abca1-deficient macrophages
Omar L Francone
Pfizer Global Research and Development, Department of Cardiovascular and Metabolic Diseases, Groton, CT 06340
Arterioscler Thromb Vasc Biol 25:1198-205. 2005
..Therefore, we examined whether the absence of ABCA1 affects the morphology, properties, and functional activities of macrophages that could be related to the development of atherosclerosis...
- ABCA1-deficient mice: insights into the role of monocyte lipid efflux in HDL formation and inflammation
Robert J Aiello
Pfizer Global Research and Development, Department of Cardiovascular and Metabolic Diseases, Eastern Point Road, Groton, Conn 06340, USA
Arterioscler Thromb Vasc Biol 23:972-80. 2003
..The phenotype of the ABCA1-deficient mouse parallels the phenotype observed in human Tangier disease, including substantial reductions in both apolipoprotein B and apolipoprotein AI with confounding affects on atherosclerosis...
The PPARα agonists fenofibrate and CP-778875 cause increased β-oxidation, leading to oxidative injury in skeletal and cardiac muscle in the ratJohn C Pettersen
Pfizer Worldwide Research and Development, Groton Laboratory, Pfizer, Inc, Groton, Connecticut 06340, USA
Toxicol Pathol 40:435-47. 2012
..Taken together, these findings were consistent with PPARα agonism and support the link between increased cardiac and skeletal muscle β-oxidation and resultant muscle injury in the rat...
- Molecular characterization of novel and selective peroxisome proliferator-activated receptor alpha agonists with robust hypolipidemic activity in vivo
Christopher D Kane
Departments of Atherosclerosis Biology, Pfizer Global Research and Development, Pfizer Inc, Groton, Connecticut 06340, USA
Mol Pharmacol 75:296-306. 2009
..Whereas these compounds are efficacious in acute preclinical models, extended safety studies and further clinical testing will be required before the full therapeutic promise of a selective PPARalpha agonist is realized...
- The hydrophobic tunnel present in LOX-1 is essential for oxidized LDL recognition and binding
Omar L Francone
Department of Atherosclerosis Biology, Pfizer Global Research and Development, Groton, CT 06340, USA
J Lipid Res 50:546-55. 2009
..These studies suggest that the central hydrophobic tunnel that extends through the entire LOX-1 molecule is a key functional domain of the receptor and is critical for the recognition of modified LDL...
- A critical role for peroxisomal proliferator-activated receptor-alpha nuclear receptors in the development of cardiomyocyte degeneration and necrosis
Ingrid Pruimboom-Brees
Pfizer Global Research and Development, Department of Cardiovascular and Metabolic Diseases, Eastern Point Rd, Groton, CT 06340, USA
Am J Pathol 169:750-60. 2006
..These findings suggest that activation of PPAR-alpha leads to increased cardiac fatty acid oxidation and subsequent accumulation of oxidative stress intermediates resulting in cardiomyocyte necrosis...
- ABCA1: regulation, function and relationship to atherosclerosis
Omar L Francone
Pfizer Global Research and Development, Groton, CT 06340, USA
Curr Opin Investig Drugs 3:415-9. 2002
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- Regulation of apoAI processing by procollagen C-proteinase enhancer-2 and bone morphogenetic protein-1
Jian Zhu
Pfizer Global Research and Development, Department of Cardiovascular and Metabolic Diseases, Groton, CT 06340, USA
J Lipid Res 50:1330-9. 2009
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- Efficacy and safety of a potent and selective peroxisome proliferator activated receptor alpha agonist in subjects with dyslipidemia and type 2 diabetes mellitus
Steven G Terra
Pfizer Global Research and Development, Groton, Connecticut, USA
Am J Cardiol 102:434-9. 2008
..In conclusion, CP-778,875 2 mg/day significantly increased HDL cholesterol, significantly lowered fasting triglycerides, and increased apoA-I and HDL subfractions. The clinical relevance of the increase in homocysteine levels is unknown...
- Increased atherosclerosis in hyperlipidemic mice with inactivation of ABCA1 in macrophages
Robert J Aiello
Pfizer Global Research and Development, Groton, Connecticut, USA
Arterioscler Thromb Vasc Biol 22:630-7. 2002
..ABCA1 deficiency in macrophages, however, demonstrates the antiatherogenic properties of ABCA1 independent of plasma lipids and HDL levels...
