Association of malondialdehyde-acetaldehyde (MAA) adducted proteins with atherosclerotic-induced vascular inflammatory injury

Gary E. Hill, Jacqueline A. Miller, Bernard Timothy Baxter, Lynell Warren Klassen, Michael J. Duryee, Dean J. Tuma, Geoffrey Milton Thiele

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Atheroscierosis is a vascular injury characterized by elevated tissue levels of tumor necrosis factor-α (TNF-α), increased expression of endothelial cell adhesion molecules, and vascular wall inflammatory cell infiltration. Foam cells are associated with atherosclerotic plaque material, and low density lipoprotein (LDL) is a lipid component of foam cells. Malondialdehyde (MDA) is an oxidative product of unsaturated fatty acids and is also present in atherosclerotic lesions. MDA-modified (adducted) proteins, including MDA-modified LDL, are present in atherosclerotic human vascular tissue. Acetaldehyde (AA) is the major metabolic product of ethanol oxidation. Both MDA and AA are highly reactive aldehydes and will combine with proteins to produce an antigenically distinct protein adduct, termed the MAA adduct. This study demonstrates that proteins modified in the presence of high concentrations of MDA can produce MAA-modified proteins in vitro. In addition, MAA adducted proteins are capable of inducing rat heart endothelial cell cultures (rHEC) to produce and release TNF-α, and cause rHEC upregulation of endothelial adhesion molecule expression, including ICAM-1. These adhesion molecules are required for circulating inflammatory cells to adhere to endothelium which allows inflammatory cell tissue infiltration. Additionally, MAA modified proteins were defected in human atherosclerotic aortic vascular tissue but not in normal aortic tissue. Since atherosclerosis is associated with an inflammatory vascular injury characterized by elevated tissue TNF-α concentrations and inflammatory cell infiltration, these data suggest that MAA-adducted proteins may be formed in atherosclerotic plaque material and may be involved in the inflammatory reaction that occurs in atherosclerosis. These data further suggest that previous studies demonstrating MDA modified protein in atherosclerotic plaque may in fact have MAA modified proteins associated with them.

Original languageEnglish (US)
Pages (from-to)107-116
Number of pages10
JournalAtherosclerosis
Volume141
Issue number1
DOIs
StatePublished - Oct 5 1998

Fingerprint

Acetaldehyde
Vascular System Injuries
Malondialdehyde
Proteins
Atherosclerotic Plaques
Blood Vessels
Foam Cells
Endothelial Cells
Tumor Necrosis Factor-alpha
LDL Lipoproteins
Atherosclerosis
Cell Culture Techniques
Cell Adhesion Molecules
Intercellular Adhesion Molecule-1
Unsaturated Fatty Acids
Aldehydes
Cell Wall
Endothelium
Ethanol
Up-Regulation

Keywords

  • Acetaldehyde
  • Atherosclerosis
  • Inflammation
  • Malondialdehyde
  • Protein adducts

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Association of malondialdehyde-acetaldehyde (MAA) adducted proteins with atherosclerotic-induced vascular inflammatory injury. / Hill, Gary E.; Miller, Jacqueline A.; Baxter, Bernard Timothy; Klassen, Lynell Warren; Duryee, Michael J.; Tuma, Dean J.; Thiele, Geoffrey Milton.

In: Atherosclerosis, Vol. 141, No. 1, 05.10.1998, p. 107-116.

Research output: Contribution to journalArticle

@article{fe2c32a448c345c3b5e4dc639329ce98,
title = "Association of malondialdehyde-acetaldehyde (MAA) adducted proteins with atherosclerotic-induced vascular inflammatory injury",
abstract = "Atheroscierosis is a vascular injury characterized by elevated tissue levels of tumor necrosis factor-α (TNF-α), increased expression of endothelial cell adhesion molecules, and vascular wall inflammatory cell infiltration. Foam cells are associated with atherosclerotic plaque material, and low density lipoprotein (LDL) is a lipid component of foam cells. Malondialdehyde (MDA) is an oxidative product of unsaturated fatty acids and is also present in atherosclerotic lesions. MDA-modified (adducted) proteins, including MDA-modified LDL, are present in atherosclerotic human vascular tissue. Acetaldehyde (AA) is the major metabolic product of ethanol oxidation. Both MDA and AA are highly reactive aldehydes and will combine with proteins to produce an antigenically distinct protein adduct, termed the MAA adduct. This study demonstrates that proteins modified in the presence of high concentrations of MDA can produce MAA-modified proteins in vitro. In addition, MAA adducted proteins are capable of inducing rat heart endothelial cell cultures (rHEC) to produce and release TNF-α, and cause rHEC upregulation of endothelial adhesion molecule expression, including ICAM-1. These adhesion molecules are required for circulating inflammatory cells to adhere to endothelium which allows inflammatory cell tissue infiltration. Additionally, MAA modified proteins were defected in human atherosclerotic aortic vascular tissue but not in normal aortic tissue. Since atherosclerosis is associated with an inflammatory vascular injury characterized by elevated tissue TNF-α concentrations and inflammatory cell infiltration, these data suggest that MAA-adducted proteins may be formed in atherosclerotic plaque material and may be involved in the inflammatory reaction that occurs in atherosclerosis. These data further suggest that previous studies demonstrating MDA modified protein in atherosclerotic plaque may in fact have MAA modified proteins associated with them.",
keywords = "Acetaldehyde, Atherosclerosis, Inflammation, Malondialdehyde, Protein adducts",
author = "Hill, {Gary E.} and Miller, {Jacqueline A.} and Baxter, {Bernard Timothy} and Klassen, {Lynell Warren} and Duryee, {Michael J.} and Tuma, {Dean J.} and Thiele, {Geoffrey Milton}",
year = "1998",
month = "10",
day = "5",
doi = "10.1016/S0021-9150(98)00153-1",
language = "English (US)",
volume = "141",
pages = "107--116",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Association of malondialdehyde-acetaldehyde (MAA) adducted proteins with atherosclerotic-induced vascular inflammatory injury

AU - Hill, Gary E.

AU - Miller, Jacqueline A.

AU - Baxter, Bernard Timothy

AU - Klassen, Lynell Warren

AU - Duryee, Michael J.

AU - Tuma, Dean J.

AU - Thiele, Geoffrey Milton

PY - 1998/10/5

Y1 - 1998/10/5

N2 - Atheroscierosis is a vascular injury characterized by elevated tissue levels of tumor necrosis factor-α (TNF-α), increased expression of endothelial cell adhesion molecules, and vascular wall inflammatory cell infiltration. Foam cells are associated with atherosclerotic plaque material, and low density lipoprotein (LDL) is a lipid component of foam cells. Malondialdehyde (MDA) is an oxidative product of unsaturated fatty acids and is also present in atherosclerotic lesions. MDA-modified (adducted) proteins, including MDA-modified LDL, are present in atherosclerotic human vascular tissue. Acetaldehyde (AA) is the major metabolic product of ethanol oxidation. Both MDA and AA are highly reactive aldehydes and will combine with proteins to produce an antigenically distinct protein adduct, termed the MAA adduct. This study demonstrates that proteins modified in the presence of high concentrations of MDA can produce MAA-modified proteins in vitro. In addition, MAA adducted proteins are capable of inducing rat heart endothelial cell cultures (rHEC) to produce and release TNF-α, and cause rHEC upregulation of endothelial adhesion molecule expression, including ICAM-1. These adhesion molecules are required for circulating inflammatory cells to adhere to endothelium which allows inflammatory cell tissue infiltration. Additionally, MAA modified proteins were defected in human atherosclerotic aortic vascular tissue but not in normal aortic tissue. Since atherosclerosis is associated with an inflammatory vascular injury characterized by elevated tissue TNF-α concentrations and inflammatory cell infiltration, these data suggest that MAA-adducted proteins may be formed in atherosclerotic plaque material and may be involved in the inflammatory reaction that occurs in atherosclerosis. These data further suggest that previous studies demonstrating MDA modified protein in atherosclerotic plaque may in fact have MAA modified proteins associated with them.

AB - Atheroscierosis is a vascular injury characterized by elevated tissue levels of tumor necrosis factor-α (TNF-α), increased expression of endothelial cell adhesion molecules, and vascular wall inflammatory cell infiltration. Foam cells are associated with atherosclerotic plaque material, and low density lipoprotein (LDL) is a lipid component of foam cells. Malondialdehyde (MDA) is an oxidative product of unsaturated fatty acids and is also present in atherosclerotic lesions. MDA-modified (adducted) proteins, including MDA-modified LDL, are present in atherosclerotic human vascular tissue. Acetaldehyde (AA) is the major metabolic product of ethanol oxidation. Both MDA and AA are highly reactive aldehydes and will combine with proteins to produce an antigenically distinct protein adduct, termed the MAA adduct. This study demonstrates that proteins modified in the presence of high concentrations of MDA can produce MAA-modified proteins in vitro. In addition, MAA adducted proteins are capable of inducing rat heart endothelial cell cultures (rHEC) to produce and release TNF-α, and cause rHEC upregulation of endothelial adhesion molecule expression, including ICAM-1. These adhesion molecules are required for circulating inflammatory cells to adhere to endothelium which allows inflammatory cell tissue infiltration. Additionally, MAA modified proteins were defected in human atherosclerotic aortic vascular tissue but not in normal aortic tissue. Since atherosclerosis is associated with an inflammatory vascular injury characterized by elevated tissue TNF-α concentrations and inflammatory cell infiltration, these data suggest that MAA-adducted proteins may be formed in atherosclerotic plaque material and may be involved in the inflammatory reaction that occurs in atherosclerosis. These data further suggest that previous studies demonstrating MDA modified protein in atherosclerotic plaque may in fact have MAA modified proteins associated with them.

KW - Acetaldehyde

KW - Atherosclerosis

KW - Inflammation

KW - Malondialdehyde

KW - Protein adducts

UR - http://www.scopus.com/inward/record.url?scp=0032487602&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032487602&partnerID=8YFLogxK

U2 - 10.1016/S0021-9150(98)00153-1

DO - 10.1016/S0021-9150(98)00153-1

M3 - Article

C2 - 9863543

AN - SCOPUS:0032487602

VL - 141

SP - 107

EP - 116

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

IS - 1

ER -