Increased vascular smooth muscle intraollular calcium responses to low density lipoprotein isolated from diabetic versus healthy subjects

J. Muthuswamv, W. O. Thompson, Scott Stevens, M. Ashraffi, M. S. Genel

Research output: Contribution to journalArticle

Abstract

Exposure of cultured vascular smooth muscle cells (VMSCs) to low density lipoprotein (LDL) stimulates a transient intracellular free calcium ([Ca ]i) response, while In vitro oxidation of LDL produces marked increases in the magnitude of the [Ca2]i elevation compared to native LDL. Since complications of diabetes have been proposed to result, in part, from increased oxidative stress and oxidized LDL has been demonstrated in vivo, we sought to determine whether LDL fron diabetics stimulates a greater [Caz ]i response in cultured VSMCs. LDL was isolated from 8 healthy and 8 Type I diabetic individuals and oxidation was measured via thiobarbituric acid reactive substances (TBARS). 20 g LDL from each individual was then used to stimulate fura-2 loaded rat VSMCs (10 cells/mL) and [Ca2]i responses were measured fluorometrically. Diabetics exhibited a 55% increase in TBARS compared to controls (p<0.001) and an approximate four-fold increase in the [Ca2+]i response to their LDL (444 nM vs. 104 nM [Ca2t]i response in diabetics and controls, respectively; p<0,025). Since increased [Ca2]i exerts both trophic and contractile effects in VSMCs, these data suggest that increased LDL oxidation may contribute to atherosclerotic disease in diabetics. Therefore, we have for the first time demonstrated, using a novel ex vivo index of atherogenicity, a significant consequence of increased LDL oxidation in a patient population. Accordingly, the ability of LDL to stimulate [Cal ]i in cultured VSMCs may serve as useful index of atherogenicity in clinical trial».

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

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Vascular Smooth Muscle
LDL Lipoproteins
Muscle
Healthy Volunteers
Calcium
Oxidation
Thiobarbituric Acid Reactive Substances
Oxidative stress
Fura-2
Diabetes Complications
Medical problems
Smooth Muscle Myocytes
Rats
Oxidative Stress
Cells
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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Increased vascular smooth muscle intraollular calcium responses to low density lipoprotein isolated from diabetic versus healthy subjects. / Muthuswamv, J.; Thompson, W. O.; Stevens, Scott; Ashraffi, M.; Genel, M. S.

In: FASEB Journal, Vol. 10, No. 3, 01.12.1996.

Research output: Contribution to journalArticle

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