Circulating levels of endothelial function are modulated by dietary monounsaturated fat
Introduction
The role of the endothelium far exceeds that of a passive barrier between the blood and subendothelial cells. It plays a unique and important role in the interface between blood and tissues. It is involved in numerous homeostatic mechanisms, such as the maintenance of a non-thrombotic surface, the metabolism of lipoproteins, participation in the regulation of vascular tone and a role in the immune response [1]. Endothelial cells produce a large number of substances involved in adhesion and transendothelial migration of circulating leucocytes into the vascular wall, as well as coagulation and fibrinolysis, all of which are involved in atherosclerotic development [2]. In vitro studies have demonstrated that the rolling of monocytes on endothelial cells is mediated by adhesion molecules, one of them, E-selectin, being a product of endothelial origin [3]. Recently, it has been shown that in vivo expression of E-selectin by the aortic endothelium is increased in atherosclerosis in hyperlipemic diabetic rabbits [4]. Another important factor is von Willebrand factor (vWF), a coagulation component. It is generally assumed that its function involves interaction with components of the subendothelium on the one hand and also interaction with platelet membrane receptors. In this case, vWF could participate in arterial thrombosis, binding to platelet membrane glycoproteins in both adhesion and aggregation, leading to thrombus formation in high shear stress rates [5]. Also, vWF has been considered as a specific endothelial product and a possible indicator of endothelial cell damage [6]. In contrast to this thrombotic function, the endothelial cells also show an active antithrombotic behaviour. One example of this is given by Tissue Factor Pathway Inhibitor (TFPI), an activated factor X dependent inhibitor of tissue-factor induced coagulation [7]. Another antithrombotic system is the natural anticoagulant mechanism dependent on the protein C-thrombomodulin mechanism. When thrombin binds to thrombomodulin, several coagulation reactions, including fibrin generation and platelet activation, are inhibited [8].
High intake of saturated fat (SAT) has been associated with an increased incidence of CHD, whereas high intake of monounsaturated fat (MUFA) has been associated with a protective effect [9], [10]. One of the mechanisms by which dietary fats can modify CHD risk is by their effect on plasma LDL and HDL cholesterol levels [11]. However, these effects do not appear to explain the magnitude of CHD protection observed in individuals living in countries with a high intake of MUFA. An additional mechanism may involve the oxidative modification of LDL particles. This process plays an important role in the initiation and progression of atherosclerosis and previous studies have shown that LDL particles obtained after a MUFA-diet have a longer lag time than particles obtained after a polyunsaturated enriched diet [12]. Furthermore, oxidative modified LDL particles could also affect endothelial cell function [13] and other non-lipid related mechanisms may also be affected by dietary fat [14]. Recently [15], we have shown that consumption of diets rich in MUFAs decreases PAI-1 plasma activity, the main physiological inhibitor of fibrinolysis, originated in hepatocytes and endothelial cells [16]. Moreover, these diets have been reported to decrease vWF in NIDDM patients [17]. These data might suggest that dietary MUFAs could modulate endothelial function. The main objective of this study was to determine the effect of a MUFA-diet, typical of Mediterranean countries, compared to an NCEP-I diet, on different soluble factors originating from endothelial cells.
Section snippets
Subjects and diets
Twenty-five healthy normolipemic (total cholesterol<5.1 mmol/l) male students attending the University of Cordoba volunteered to participate in the study. All had a comprehensive medical history, physical examination and clinical chemistry analysis before enrolment. Subjects under 30 years of age with total cholesterol plasma levels lower than 5.1 mmol/l on their usual diets, with no evidence of any chronic illness (such as hepatic, renal, thyroid, or cardiac dysfunction), or unusually high
Results
The age, BMI and basal plasma lipid levels and apolipoprotein levels of the 25 subjects who participated in the study are presented in Table 1. Dietary composition was analyzed in duplicate. The values obtained (Table 2) were similar to those calculated from the tables. Analysis of the fatty acid composition of the LDL-C esters for each of the diet phases (Table 3) demonstrated a significant increase in palmitic acid during the dietary period rich in saturated fats compared to the other two
Discussion
The present study shows for the first time that after consumption of a MUFA-diet by healthy young men for 28 days, both vWF plasma activity and total TFPI plasma concentration were significantly lower compared with levels recorded after the periods in which the same subjects consumed a low-fat carbohydrate-rich diet or a high SAT-diet, suggesting that a MUFA-diet might beneficially affect endothelial function. We also confirmed our previous results which found a decrease in PAI-1 plasma levels
Acknowledgements
This work was supported by research grants from the Comisión Interministerial de Ciencia y Tecnologı́a, Plan Nacional I+D, Spain (no. OLI96/2146 and no. SAF96-0060 to F. Pérez-Jiménez), the Spanish Ministry of Health (FIS 94/1547, 93/0746, 95/1144, 96/1540, 98/1531 to J. López-Miranda), Consejerı́a de Salud, Servicio Andaluz de Salud (PAI 96-54, 97), The National Institute of Health, Bethesda, MD (HL 54776 to J.M. Ordovas) and Fundación Cultural Hospital Reina Sofı́a (P. Castro). We thank all
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