title: Is it just paraoxonase 1 or are other members of the paraoxonase gene family implicated in atherosclerosis?
abstract: OBJECTIVE
  During the past decade, paraoxonase 1, a HDL-associated protein, has been demonstrated to be an important contributor to the antioxidant capacity of HDL. Studies using paraoxonase 1 null mice by gene targeting and transgenic mice corroborated the hypothesis that paraoxonase 1 protects against atherosclerosis. In contrast to paraoxonase 1, the other two members of the paraoxonase gene family, namely paraoxonase 2 and paraoxonase 3, are either undetectable (paraoxonase 2) or detected at very low levels (paraoxonase 3) on HDL, and are considered to participate in intracellular antioxidant mechanisms. In this review, we summarize studies reported in the past 2 years suggesting a protective role for paraoxonase 2 and paraoxonase 3 in the development of atherosclerosis in mice.
  
  
  RESULTS
  Adenovirus-mediated expression of human paraoxonase 2 or paraoxonase 3 proteins protects against the development of atherosclerosis in apolipoprotein E-deficient mice. Paraoxonase 2-deficient mice develop significantly larger atherosclerotic lesions than their wild-type and heterozygous counterparts on an atherogenic diet despite having lower levels of apolipoprotein B-containing lipoproteins. Atherosclerotic lesions were significantly lower in male hPON3Tg/LDLR null mice than in LDLR null mice on a western diet.
  
  
  CONCLUSIONS
  We conclude that, in addition to paraoxonase 1, both paraoxonase 2 and paraoxonase 3 proteins are protective against the development of atherosclerosis in mice. These findings underscore the utility of all members of the paraoxonase gene family as therapeutic targets for the treatment of atherosclerosis.
authors.affiliation: Department of Medicine/Cardiology, University of California Los Angeles, Los Angeles, CA 90095, USA. sreddy@mednet.ucla.edu
authors.forename: Srinivasa T
authors.initials: ST
authors.lastname: Reddy
authors.forename: Asokan
authors.initials: A
authors.lastname: Devarajan
authors.forename: Noam
authors.initials: N
authors.lastname: Bourquard
authors.forename: Diana
authors.initials: D
authors.lastname: Shih
authors.forename: Alan M
authors.initials: AM
authors.lastname: Fogelman
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism*; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D006801:Humans
chemical_list: D043303:Aryldialkylphosphatase