Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy subjects
Open Access
- 16 February 2010
- journal article
- Published by Springer Science and Business Media LLC in Cardiovascular Diabetology
- Vol. 9 (1), 9
- https://doi.org/10.1186/1475-2840-9-9
Abstract
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. 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). 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 ≥ 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 ≤ 0.01). The FFA-induced increase was independent from the degree of adiposity, being of similar magnitude in lean, overweight and obese subjects. 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.Keywords
This publication has 68 references indexed in Scilit:
- Inflammatory markers in relation to insulin resistance and the metabolic syndromeEuropean Journal of Clinical Investigation, 2008
- Serum Myeloperoxidase Levels Are Associated With the Future Risk of Coronary Artery Disease in Apparently Healthy IndividualsJournal of the American College of Cardiology, 2007
- Inflammation and insulin resistanceJCI Insight, 2006
- Elevated Concentrations of Nonesterified Fatty Acids Increase Monocyte Expression of CD11b and Adhesion to Endothelial CellsArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- Metabolic syndrome aggravates the increased endothelial activation and low‐grade inflammation in subjects with familial low HDLAnnals of Medicine, 2006
- Levels of soluble adhesion molecules in various clinical presentations of coronary atherosclerosisInternational Journal of Cardiology, 2004
- Fatty Acid Metabolism and Vascular DiseaseTrends in Cardiovascular Medicine, 2004
- Soluble E-selectin in cardiovascular disease and its risk factorsThrombosis and Haemostasis, 2003
- Association of angiotensin converting enzyme and plasminogen activator inhibitor-1 promoter gene polymorphisms with features of the insulin resistance syndrome in patients with premature coronary heart diseaseAtherosclerosis, 2001
- Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions.JCI Insight, 1994