Peroxisome proliferator-activated receptor-alpha and atherosclerosis: From basic mechanisms to clinical implications

Zarmen Israelian-Konaraki, Peter D. Reaven

Research output: Contribution to journalReview article

39 Citations (Scopus)

Abstract

Atherosclerosis is an inflammatory process triggered by the presence of lipids in the vascular wall and encompasses a complex interaction between inflammatory cells, vascular elements and lipoproteins through the expression of several adhesion molecules and cytokines. Activation of the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) has been demonstrated to modulate many aspects of lipoprotein metabolism and inflammation in vitro as well as in animal and human studies. The tissue distribution of PPAR-α is extensive and it is abundantly present in the vascular wall where it may mediate many of anti-inflammatory and antiatherogenic effects. Major clinical trials, such as the Veterans Affairs High-Density Lipoprotein Intervention Trial, the Helsinki Heart Study and the Diabetes Atherosclerosis Intervention Study, have demonstrated the beneficial effects of synthetic agonists of PPAR-α, specifically fibric acid derivatives, on cardiovascular disease outcome. Although fibric acid trials have reported cardiovascular risk reduction in patients with dyslipidemia, the favorable alterations in plasma lipids can only partially explain the reduction in cardiovascular events in these studies. One common link among these trials was a cohort with a high prevalence of insulin resistance or diabetes, conditions associated with heightened systemic inflammation and increased risk for development and progression of atherosclerosis. In this paper, we will review the many antiatherogenic effects of PPAR-α ligands and evidence from fibric acid trials that individuals with insulin resistance or diabetes benefit the most from these drugs, consistent with their anti-inflammatory and antithrombotic properties.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalCardiology
Volume103
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

Fingerprint

PPAR alpha
Peroxisome Proliferator-Activated Receptors
Atherosclerosis
Blood Vessels
Lipoproteins
Insulin Resistance
Anti-Inflammatory Agents
Inflammation
Lipids
Fibric Acids
Veterans
Tissue Distribution
Risk Reduction Behavior
HDL Lipoproteins
Cytoplasmic and Nuclear Receptors
Dyslipidemias
Cardiovascular Diseases
Clinical Trials
Cytokines
Ligands

Keywords

  • Atherosclerosis
  • Cardiovascular disease
  • Fibric acids
  • Inflammation
  • Peroxisome proliferator-activated receptor-α

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

Peroxisome proliferator-activated receptor-alpha and atherosclerosis : From basic mechanisms to clinical implications. / Israelian-Konaraki, Zarmen; Reaven, Peter D.

In: Cardiology, Vol. 103, No. 1, 01.01.2005, p. 1-9.

Research output: Contribution to journalReview article

@article{c1887b52089245a6bdbc166b37af2426,
title = "Peroxisome proliferator-activated receptor-alpha and atherosclerosis: From basic mechanisms to clinical implications",
abstract = "Atherosclerosis is an inflammatory process triggered by the presence of lipids in the vascular wall and encompasses a complex interaction between inflammatory cells, vascular elements and lipoproteins through the expression of several adhesion molecules and cytokines. Activation of the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) has been demonstrated to modulate many aspects of lipoprotein metabolism and inflammation in vitro as well as in animal and human studies. The tissue distribution of PPAR-α is extensive and it is abundantly present in the vascular wall where it may mediate many of anti-inflammatory and antiatherogenic effects. Major clinical trials, such as the Veterans Affairs High-Density Lipoprotein Intervention Trial, the Helsinki Heart Study and the Diabetes Atherosclerosis Intervention Study, have demonstrated the beneficial effects of synthetic agonists of PPAR-α, specifically fibric acid derivatives, on cardiovascular disease outcome. Although fibric acid trials have reported cardiovascular risk reduction in patients with dyslipidemia, the favorable alterations in plasma lipids can only partially explain the reduction in cardiovascular events in these studies. One common link among these trials was a cohort with a high prevalence of insulin resistance or diabetes, conditions associated with heightened systemic inflammation and increased risk for development and progression of atherosclerosis. In this paper, we will review the many antiatherogenic effects of PPAR-α ligands and evidence from fibric acid trials that individuals with insulin resistance or diabetes benefit the most from these drugs, consistent with their anti-inflammatory and antithrombotic properties.",
keywords = "Atherosclerosis, Cardiovascular disease, Fibric acids, Inflammation, Peroxisome proliferator-activated receptor-α",
author = "Zarmen Israelian-Konaraki and Reaven, {Peter D.}",
year = "2005",
month = "1",
day = "1",
doi = "10.1159/000081845",
language = "English (US)",
volume = "103",
pages = "1--9",
journal = "Cardiology",
issn = "0008-6312",
publisher = "S. Karger AG",
number = "1",

}

TY - JOUR

T1 - Peroxisome proliferator-activated receptor-alpha and atherosclerosis

T2 - From basic mechanisms to clinical implications

AU - Israelian-Konaraki, Zarmen

AU - Reaven, Peter D.

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Atherosclerosis is an inflammatory process triggered by the presence of lipids in the vascular wall and encompasses a complex interaction between inflammatory cells, vascular elements and lipoproteins through the expression of several adhesion molecules and cytokines. Activation of the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) has been demonstrated to modulate many aspects of lipoprotein metabolism and inflammation in vitro as well as in animal and human studies. The tissue distribution of PPAR-α is extensive and it is abundantly present in the vascular wall where it may mediate many of anti-inflammatory and antiatherogenic effects. Major clinical trials, such as the Veterans Affairs High-Density Lipoprotein Intervention Trial, the Helsinki Heart Study and the Diabetes Atherosclerosis Intervention Study, have demonstrated the beneficial effects of synthetic agonists of PPAR-α, specifically fibric acid derivatives, on cardiovascular disease outcome. Although fibric acid trials have reported cardiovascular risk reduction in patients with dyslipidemia, the favorable alterations in plasma lipids can only partially explain the reduction in cardiovascular events in these studies. One common link among these trials was a cohort with a high prevalence of insulin resistance or diabetes, conditions associated with heightened systemic inflammation and increased risk for development and progression of atherosclerosis. In this paper, we will review the many antiatherogenic effects of PPAR-α ligands and evidence from fibric acid trials that individuals with insulin resistance or diabetes benefit the most from these drugs, consistent with their anti-inflammatory and antithrombotic properties.

AB - Atherosclerosis is an inflammatory process triggered by the presence of lipids in the vascular wall and encompasses a complex interaction between inflammatory cells, vascular elements and lipoproteins through the expression of several adhesion molecules and cytokines. Activation of the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) has been demonstrated to modulate many aspects of lipoprotein metabolism and inflammation in vitro as well as in animal and human studies. The tissue distribution of PPAR-α is extensive and it is abundantly present in the vascular wall where it may mediate many of anti-inflammatory and antiatherogenic effects. Major clinical trials, such as the Veterans Affairs High-Density Lipoprotein Intervention Trial, the Helsinki Heart Study and the Diabetes Atherosclerosis Intervention Study, have demonstrated the beneficial effects of synthetic agonists of PPAR-α, specifically fibric acid derivatives, on cardiovascular disease outcome. Although fibric acid trials have reported cardiovascular risk reduction in patients with dyslipidemia, the favorable alterations in plasma lipids can only partially explain the reduction in cardiovascular events in these studies. One common link among these trials was a cohort with a high prevalence of insulin resistance or diabetes, conditions associated with heightened systemic inflammation and increased risk for development and progression of atherosclerosis. In this paper, we will review the many antiatherogenic effects of PPAR-α ligands and evidence from fibric acid trials that individuals with insulin resistance or diabetes benefit the most from these drugs, consistent with their anti-inflammatory and antithrombotic properties.

KW - Atherosclerosis

KW - Cardiovascular disease

KW - Fibric acids

KW - Inflammation

KW - Peroxisome proliferator-activated receptor-α

UR - http://www.scopus.com/inward/record.url?scp=9144271375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9144271375&partnerID=8YFLogxK

U2 - 10.1159/000081845

DO - 10.1159/000081845

M3 - Review article

C2 - 15528894

AN - SCOPUS:9144271375

VL - 103

SP - 1

EP - 9

JO - Cardiology

JF - Cardiology

SN - 0008-6312

IS - 1

ER -