Of Cows, Sheep, and Cardiovascular Disease

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Of Cows, Sheep, and Cardiovascular Disease

• HDL and Paraoxonase

Darrell Rubin, MD PhD Department of Internal
Medicine UH Case Medical Center
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Lenz et al Toxicology 233 31, 2007
Photos from the BBC
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Overview

• Review the relationship between HDL and CVD
• Discuss the structure and function of paraoxonase
• Discuss the relationship between paraoxonase and
  CVD
• Discuss interventions that affect paraoxonase
  activity

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Reverse Cholesterol Transport
MPO
Adapted from Movva et al Clin Chem 54(5)
788-800, 2008
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HDL and Risk of CVD
Castelli et al JAMA 256(20) 2835-38, 1986
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HDL Properties
Adapted from Movva et al Clin Chem 54(5)
788-800, 2008
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HDL Binding Partners
Vaisar et al JCI 117(3) 746, 2007
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Overview

• Review the relationship between HDL and CVD
• Discuss the structure and function of paraoxonase
• Discuss the relationship between paraoxonase and
  CVD
• Discuss interventions that affect paraoxonase
  activity

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PON structure and function
James et al. Free Rad Biol Med 37(12) 1986,
2004
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PON expression
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PON substrates
Billecke et al Drug Metab and Dispo 28(11) 1335,
2000
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PON

• What is PON?
• Gene family
• polymorphisms
• substrates

Costa et al Biochem Pharm 69 541-550, 2005
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Overview

• Review the relationship between HDL and CVD
• Discuss the structure and function of paraoxonase
• Discuss the relationship between paraoxonase and
  CVD
• Discuss interventions that affect paraoxonase
  activity

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PON and CVD
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PON and CVD
McElveen Clin Chem 32(4) 671-3, 1986
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Prospective cohort study Men 49 65 years of
age Recruitment 1984 1988 15 year follow up
Mackness et al Circulation 107 2775-2779, 2003
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Graner et al JACC 47(12) 2429, 2006
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Bhattacharyya et al Jama 299(11) 1265, 2008
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Bhattacharyya et al Jama 299(11) 1265, 2008
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Compare and Contrast
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Overview

• Review the relationship between HDL and CVD
• Discuss the structure and function of paraoxonase
• Discuss the relationship between paraoxonase and
  CVD
• Discuss interventions that affect paraoxonase
  activity

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Costa et al Biochem Pharm 69 541-550, 2005
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Summary

• HDL has many associated proteins and functions
  which
• seem to be important in the development of
  atherosclerosis.
• PON function has been associated with protection
  against
• atherosclerosis.
• PON function can be modified.