Low-density lipoprotein postsecretory modification, monocyte function, and circulating adhesion molecules in type 2 diabetic patients with and without macrovascular complications: The effect of α-tocopherol supplementation

S. Devaraj, I. Jialal

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Background - Although diabetes confers an increased propensity toward accelerated atherogenesis, data are lacking on monocyte activity in type 2 diabetic patients with (DM2-MV) and without (DM2) macrovascular disease compared with control subjects. Thus, we tested whether (1) postsecretory modifications of LDL (glycation and oxidation), monocyte proatherogenic activity, and circulating levels of soluble cell adhesion molecules (sCAMs) are more pronounced in DM2-MV than in DM2 and control subjects and (2) RRR- α-tocopherol (AT) therapy, 1200 IU/d for 3 months, has a similar effect in the 3 groups (n=25 per group). Methods and Results - Although LDL glycation was increased in both diabetic groups compared with control subjects. AT therapy had no significant effect on glycation. AT therapy significantly decreased LDL oxidizability in all 3 groups. Diabetic monocytes released significantly more superoxide anion (O2 -) and interleukin-1β (IL-1β) and exhibited greater adhesion to endothelium than control subjects. AT therapy significantly decreased the release of O2 -, IL-1β, tumor necrosis factor- α, and monocyte-endothelium adhesion in all 3 groups. There was no significant difference between the 2 diabetic groups for any of the above parameters. sICAM levels were significantly elevated in both diabetic groups compared with controls. AT therapy resulted in a significant decrease in sCAMs. Conclusions - This is the first demonstration of increased IL-1β secretion and increased adhesion of monocytes to endothelium from normotriglyceridemic diabetic subjects and of decreased monocyte activity and sCAMs with AT therapy in diabetic subjects with and without macrovasculopathy.

Original languageEnglish (US)
Pages (from-to)191-196
Number of pages6
JournalCirculation
Volume102
Issue number2
StatePublished - Jul 11 2000
Externally publishedYes

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Tocopherols
LDL Lipoproteins
Monocytes
Cell Adhesion Molecules
Interleukin-1
Endothelium
Therapeutics
Superoxides
Atherosclerosis
Tumor Necrosis Factor-alpha

Keywords

  • Cell adhesion molecules
  • Cells
  • Diabetes
  • Proteins
  • Vitamins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Low-density lipoprotein postsecretory modification, monocyte function, and circulating adhesion molecules in type 2 diabetic patients with and without macrovascular complications: The effect of α-tocopherol supplementation",
abstract = "Background - Although diabetes confers an increased propensity toward accelerated atherogenesis, data are lacking on monocyte activity in type 2 diabetic patients with (DM2-MV) and without (DM2) macrovascular disease compared with control subjects. Thus, we tested whether (1) postsecretory modifications of LDL (glycation and oxidation), monocyte proatherogenic activity, and circulating levels of soluble cell adhesion molecules (sCAMs) are more pronounced in DM2-MV than in DM2 and control subjects and (2) RRR- α-tocopherol (AT) therapy, 1200 IU/d for 3 months, has a similar effect in the 3 groups (n=25 per group). Methods and Results - Although LDL glycation was increased in both diabetic groups compared with control subjects. AT therapy had no significant effect on glycation. AT therapy significantly decreased LDL oxidizability in all 3 groups. Diabetic monocytes released significantly more superoxide anion (O2 -) and interleukin-1β (IL-1β) and exhibited greater adhesion to endothelium than control subjects. AT therapy significantly decreased the release of O2 -, IL-1β, tumor necrosis factor- α, and monocyte-endothelium adhesion in all 3 groups. There was no significant difference between the 2 diabetic groups for any of the above parameters. sICAM levels were significantly elevated in both diabetic groups compared with controls. AT therapy resulted in a significant decrease in sCAMs. Conclusions - This is the first demonstration of increased IL-1β secretion and increased adhesion of monocytes to endothelium from normotriglyceridemic diabetic subjects and of decreased monocyte activity and sCAMs with AT therapy in diabetic subjects with and without macrovasculopathy.",
keywords = "Cell adhesion molecules, Cells, Diabetes, Proteins, Vitamins",
author = "S. Devaraj and I. Jialal",
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T1 - Low-density lipoprotein postsecretory modification, monocyte function, and circulating adhesion molecules in type 2 diabetic patients with and without macrovascular complications

T2 - The effect of α-tocopherol supplementation

AU - Devaraj, S.

AU - Jialal, I.

PY - 2000/7/11

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N2 - Background - Although diabetes confers an increased propensity toward accelerated atherogenesis, data are lacking on monocyte activity in type 2 diabetic patients with (DM2-MV) and without (DM2) macrovascular disease compared with control subjects. Thus, we tested whether (1) postsecretory modifications of LDL (glycation and oxidation), monocyte proatherogenic activity, and circulating levels of soluble cell adhesion molecules (sCAMs) are more pronounced in DM2-MV than in DM2 and control subjects and (2) RRR- α-tocopherol (AT) therapy, 1200 IU/d for 3 months, has a similar effect in the 3 groups (n=25 per group). Methods and Results - Although LDL glycation was increased in both diabetic groups compared with control subjects. AT therapy had no significant effect on glycation. AT therapy significantly decreased LDL oxidizability in all 3 groups. Diabetic monocytes released significantly more superoxide anion (O2 -) and interleukin-1β (IL-1β) and exhibited greater adhesion to endothelium than control subjects. AT therapy significantly decreased the release of O2 -, IL-1β, tumor necrosis factor- α, and monocyte-endothelium adhesion in all 3 groups. There was no significant difference between the 2 diabetic groups for any of the above parameters. sICAM levels were significantly elevated in both diabetic groups compared with controls. AT therapy resulted in a significant decrease in sCAMs. Conclusions - This is the first demonstration of increased IL-1β secretion and increased adhesion of monocytes to endothelium from normotriglyceridemic diabetic subjects and of decreased monocyte activity and sCAMs with AT therapy in diabetic subjects with and without macrovasculopathy.

AB - Background - Although diabetes confers an increased propensity toward accelerated atherogenesis, data are lacking on monocyte activity in type 2 diabetic patients with (DM2-MV) and without (DM2) macrovascular disease compared with control subjects. Thus, we tested whether (1) postsecretory modifications of LDL (glycation and oxidation), monocyte proatherogenic activity, and circulating levels of soluble cell adhesion molecules (sCAMs) are more pronounced in DM2-MV than in DM2 and control subjects and (2) RRR- α-tocopherol (AT) therapy, 1200 IU/d for 3 months, has a similar effect in the 3 groups (n=25 per group). Methods and Results - Although LDL glycation was increased in both diabetic groups compared with control subjects. AT therapy had no significant effect on glycation. AT therapy significantly decreased LDL oxidizability in all 3 groups. Diabetic monocytes released significantly more superoxide anion (O2 -) and interleukin-1β (IL-1β) and exhibited greater adhesion to endothelium than control subjects. AT therapy significantly decreased the release of O2 -, IL-1β, tumor necrosis factor- α, and monocyte-endothelium adhesion in all 3 groups. There was no significant difference between the 2 diabetic groups for any of the above parameters. sICAM levels were significantly elevated in both diabetic groups compared with controls. AT therapy resulted in a significant decrease in sCAMs. Conclusions - This is the first demonstration of increased IL-1β secretion and increased adhesion of monocytes to endothelium from normotriglyceridemic diabetic subjects and of decreased monocyte activity and sCAMs with AT therapy in diabetic subjects with and without macrovasculopathy.

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