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Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy subjects.

Mathew M, Tay E, Cusi K - Cardiovasc Diabetol (2010)

Bottom Line: Elevated plasma FFA increased plasma markers of endothelial activation ICAM-1 (138 +/- 10 vs. 186 +/- 25 ng/ml), VCAM-1 (1066 +/- 67 vs. 1204 +/- 65 ng/ml) and sE-S (20 +/- 1 vs. 24 +/- 1 ng/ml) between 13-35% and by > or = 2-fold plasma levels of myeloperoxidase (7.5 +/- 0.9 to 15 +/- 25 ng/ml), an inflammatory marker of future CVD, and tPAI-1 (9.7 +/- 0.6 to 22.5 +/- 1.5 ng/ml), an indicator of a prothrombotic state (all p < or = 0.01).The FFA-induced increase was independent from the degree of adiposity, being of similar magnitude in lean, overweight and obese subjects.This suggests that even transient (48-hour) and modest increases in plasma FFA may initiate early vascular abnormalities that promote atherosclerosis and CVD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Diabetes Division, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas-78229, USA.

ABSTRACT

Background: CVD in obesity and T2DM are associated with endothelial activation, elevated plasma vascular inflammation markers and a prothrombotic state. We examined the contribution of FFA to these abnormalities following a 48-hour physiological increase in plasma FFA to levels of obesity and diabetes in a group of healthy subjects.

Methods: 40 non-diabetic subjects (age = 38 +/- 3 yr, BMI = 28 +/- 1 kg/m2, FPG = 95 +/- 1 mg/dl, HbA1c = 5.3 +/- 0.1%) were admitted twice and received a 48-hour infusion of normal saline or low-dose lipid. Plasma was drawn for intracellular (ICAM-1) and vascular (VCAM-1) adhesion molecules-1, E-selectin (sE-S), myeloperoxidase (MPO) and total plasminogen inhibitor-1 (tPAI-1). Insulin sensitivity was measured by a hyperglycemic clamp (M/I).

Results: Lipid infusion increased plasma FFA to levels observed in obesity and T2DM and reduced insulin sensitivity by 27% (p = 0.01). Elevated plasma FFA increased plasma markers of endothelial activation ICAM-1 (138 +/- 10 vs. 186 +/- 25 ng/ml), VCAM-1 (1066 +/- 67 vs. 1204 +/- 65 ng/ml) and sE-S (20 +/- 1 vs. 24 +/- 1 ng/ml) between 13-35% and by > or = 2-fold plasma levels of myeloperoxidase (7.5 +/- 0.9 to 15 +/- 25 ng/ml), an inflammatory marker of future CVD, and tPAI-1 (9.7 +/- 0.6 to 22.5 +/- 1.5 ng/ml), an indicator of a prothrombotic state (all p < or = 0.01). The FFA-induced increase was independent from the degree of adiposity, being of similar magnitude in lean, overweight and obese subjects.

Conclusions: An increase in plasma FFA within the physiological range observed in obesity and T2DM induces markers of endothelial activation, vascular inflammation and thrombosis in healthy subjects. This suggests that even transient (48-hour) and modest increases in plasma FFA may initiate early vascular abnormalities that promote atherosclerosis and CVD.

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Compared to a saline, FFA increased doubled plasma MPO from 7.5 ± 0.9 to 15 ± 25 ng/ml (p = 0.01) and tPAI-1 by 132% from 9.7 ± 0.6 to 22.5 ± 1.5 ng/ml (p < 0.001)
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Figure 3: Compared to a saline, FFA increased doubled plasma MPO from 7.5 ± 0.9 to 15 ± 25 ng/ml (p = 0.01) and tPAI-1 by 132% from 9.7 ± 0.6 to 22.5 ± 1.5 ng/ml (p < 0.001)

Mentions: Plasma MPO and tPAI-1 levels were also altered by FFA elevation and to a greater extent. Compared to a saline, FFA increased doubled plasma MPO from 7.5 ± 0.9 to 15 ± 25 ng/ml (p = 0.01) and tPAI-1 by 132% from 9.7 ± 0.6 to 22.5 ± 1.5 ng/ml (p < 0.001) (Figure 3). Figure 4 summarizes the percent increase with lipid infusion of markers of endothelial activation, MPO and tPAI-1. The increase in plasma FFA achieved with lipid correlated very strongly (r = 0.69, p < 0.001) with the increase in plasma tPAI-1, suggesting a close relationship between FFA and induction of a prothrombotic state under these experimental conditions.


Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy subjects.

Mathew M, Tay E, Cusi K - Cardiovasc Diabetol (2010)

Compared to a saline, FFA increased doubled plasma MPO from 7.5 ± 0.9 to 15 ± 25 ng/ml (p = 0.01) and tPAI-1 by 132% from 9.7 ± 0.6 to 22.5 ± 1.5 ng/ml (p < 0.001)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2837624&req=5

Figure 3: Compared to a saline, FFA increased doubled plasma MPO from 7.5 ± 0.9 to 15 ± 25 ng/ml (p = 0.01) and tPAI-1 by 132% from 9.7 ± 0.6 to 22.5 ± 1.5 ng/ml (p < 0.001)
Mentions: Plasma MPO and tPAI-1 levels were also altered by FFA elevation and to a greater extent. Compared to a saline, FFA increased doubled plasma MPO from 7.5 ± 0.9 to 15 ± 25 ng/ml (p = 0.01) and tPAI-1 by 132% from 9.7 ± 0.6 to 22.5 ± 1.5 ng/ml (p < 0.001) (Figure 3). Figure 4 summarizes the percent increase with lipid infusion of markers of endothelial activation, MPO and tPAI-1. The increase in plasma FFA achieved with lipid correlated very strongly (r = 0.69, p < 0.001) with the increase in plasma tPAI-1, suggesting a close relationship between FFA and induction of a prothrombotic state under these experimental conditions.

Bottom Line: Elevated plasma FFA increased plasma markers of endothelial activation ICAM-1 (138 +/- 10 vs. 186 +/- 25 ng/ml), VCAM-1 (1066 +/- 67 vs. 1204 +/- 65 ng/ml) and sE-S (20 +/- 1 vs. 24 +/- 1 ng/ml) between 13-35% and by > or = 2-fold plasma levels of myeloperoxidase (7.5 +/- 0.9 to 15 +/- 25 ng/ml), an inflammatory marker of future CVD, and tPAI-1 (9.7 +/- 0.6 to 22.5 +/- 1.5 ng/ml), an indicator of a prothrombotic state (all p < or = 0.01).The FFA-induced increase was independent from the degree of adiposity, being of similar magnitude in lean, overweight and obese subjects.This suggests that even transient (48-hour) and modest increases in plasma FFA may initiate early vascular abnormalities that promote atherosclerosis and CVD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Diabetes Division, Department of Medicine, The University of Texas Health Science Center at San Antonio, Texas-78229, USA.

ABSTRACT

Background: CVD in obesity and T2DM are associated with endothelial activation, elevated plasma vascular inflammation markers and a prothrombotic state. We examined the contribution of FFA to these abnormalities following a 48-hour physiological increase in plasma FFA to levels of obesity and diabetes in a group of healthy subjects.

Methods: 40 non-diabetic subjects (age = 38 +/- 3 yr, BMI = 28 +/- 1 kg/m2, FPG = 95 +/- 1 mg/dl, HbA1c = 5.3 +/- 0.1%) were admitted twice and received a 48-hour infusion of normal saline or low-dose lipid. Plasma was drawn for intracellular (ICAM-1) and vascular (VCAM-1) adhesion molecules-1, E-selectin (sE-S), myeloperoxidase (MPO) and total plasminogen inhibitor-1 (tPAI-1). Insulin sensitivity was measured by a hyperglycemic clamp (M/I).

Results: Lipid infusion increased plasma FFA to levels observed in obesity and T2DM and reduced insulin sensitivity by 27% (p = 0.01). Elevated plasma FFA increased plasma markers of endothelial activation ICAM-1 (138 +/- 10 vs. 186 +/- 25 ng/ml), VCAM-1 (1066 +/- 67 vs. 1204 +/- 65 ng/ml) and sE-S (20 +/- 1 vs. 24 +/- 1 ng/ml) between 13-35% and by > or = 2-fold plasma levels of myeloperoxidase (7.5 +/- 0.9 to 15 +/- 25 ng/ml), an inflammatory marker of future CVD, and tPAI-1 (9.7 +/- 0.6 to 22.5 +/- 1.5 ng/ml), an indicator of a prothrombotic state (all p < or = 0.01). The FFA-induced increase was independent from the degree of adiposity, being of similar magnitude in lean, overweight and obese subjects.

Conclusions: An increase in plasma FFA within the physiological range observed in obesity and T2DM induces markers of endothelial activation, vascular inflammation and thrombosis in healthy subjects. This suggests that even transient (48-hour) and modest increases in plasma FFA may initiate early vascular abnormalities that promote atherosclerosis and CVD.

Show MeSH
Related in: MedlinePlus