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(Circulation Research. 2007;100:1104.)
© 2007 American Heart Association, Inc.

Editorials

Human PON3, Effects Beyond the HDL

Clues From Human PON3 Transgenic Mice

Dragomir I. Draganov

From the Department of Metabolism, WIL Research Laboratories, LLC, Ashland, Ohio.

Correspondence to Dragomir I. Draganov, WIL Research Laboratories, LLC, 1407 George Road, Ashland, OH 44805. E-mail ddraganov@wilresearch.com

See related article, pages 1200–1207

Key Words: lactonase • PON3 • interspecies differences

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The article by Shih et al¹ in this issue of Circulation Research is the first report of transgenic expression of human Paraoxonase 3 (PON3) in mice and its ability to decrease significantly atherosclerotic lesion formation and adiposity. These effects were, interestingly, observed only in male but not in female mice on either C57BL/6J or LDLR KO backgrounds. Noteworthy, no human or mouse PON3 were detected in mouse HDL and plasma and therefore the effects of human PON3 were derived from PON3 in the tissues, not in the blood.

PON3 is a member of the PON gene family that includes PON1, PON2, and PON3.² PON enzymes are well conserved in mammals: at the amino acid level, the orthologs share 79% to 95% and the paralogs 65% identity.^2,3 PON1, PON2 and PON3, have different cell and tissue distribution as well as different regulation of expression, suggesting distinct physiological roles for each of them. These roles, however, remain largely unknown. Phylogenetic, structural and biochemical data demonstrate that all three PONs are primarily lactone hydrolyzing enzymes, albeit with different substrate specificity.^3–5 PON1 is by far the most studied member of the family, and much of our understanding of the PON enzymes is derived primarily from studies involving PON1 protein. PON1 is synthesized in the liver and secreted in the blood where it associates almost exclusively with the HDL fraction. There is ample evidence from in vitro, animal and epidemiological studies that PON1 protects against atherosclerosis^6,7; however, the exact mechanisms are . . . [Full Text of this Article]

Related Article:

Decreased Obesity and Atherosclerosis in Human Paraoxonase 3 Transgenic Mice

Diana M. Shih, Yu-Rong Xia, Xu-Ping Wang, Susanna S. Wang, Noam Bourquard, Alan M. Fogelman, Aldons J. Lusis, and Srinivasa T. Reddy
Circ. Res. 2007 100: 1200-1207. [Abstract] [Full Text] [PDF]

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