Atherosclerosis 145 (1999) 351 – 358 Circulating levels of endothelial function are modulated by dietary monounsaturated fat Francisco Pe ´rez-Jime ´nez a, *, Pedro Castro a , Jose ´ Lo ´ pez-Miranda a , Elier Paz-Rojas a , Angeles Blanco a , Fernando Lo ´ pez-Segura a , Francisco Velasco b , Carmen Marı ´n a , Francisco Fuentes a , Jose ´ M. Ordova ´s c a Unidad de Lı ´pidos y Arteriosclerosis, Hospital Uniersitario Reina Sofia, Ada Mene ´ndez Pidal, s /n 14004, Co ´rdoba, Spain b Sericio de Hematologı ´a, Hospital Uniersitario Reina Sofia, Ada Mene ´ndez Pidal, s /n 14004, Co ´rdoba, Spain c Lipid Metabolism Laboratory, US Department of Agriculture, human Nutrition Research Centre on Aging at Tufts Uniersity, Boston, MA0211, USA Received 21 January 1998; received in revised form 16 December 1998; accepted 22 February 1999 Abstract Background : For the most part, the benefits of monounsaturated-rich diets (MUFA-diet) have been related to their action on plasma lipid levels. However other non-lipidic effects could also be involved in their protective effects. One of these involves the decrease in plasma levels of plasminogen activator inhibitor type 1 (PAI-1), the main inhibitor of fibrinolysis. Given that the PAI-1 is of endothelial origin, one hypothesis is that the MUFA-diet could protect against CHD by modulating some endothelial components. Methods and results : Healthy male subjects (n =25) received three different consecutive diets, each lasting 28 days: a low fat NCEP-I-diet, with 28% calories as fat, 10% saturated fat (SAT), 12% monounsaturated (MUFA) and 6% polyunsatu- rated (PUFA); a MUFA-diet, with 38% calories as fat, 10% SAT, 22% MUFA and 6% PUFA; and a SAT rich-diet (SAT-diet), with 38% calories as fat, 20% SAT, 12% MUFA and 6% PUFA. After each dietary period, the plasma lipid profile was determined, including total cholesterol, HDL cholesterol, LDL cholesterol, total triglyceride, apo A1, apo B plasma levels and conjugated diene formation, after incubation of LDL particles with Cu 5 M/l. Endothelial products measured in plasma were von Willebrand factor (vWF), E-selectin, Thrombomodulin and Tissue Factor Pathway Inhibitor (TFPI) levels. We observed a decrease in vWF, PAI-1 and TFPI plasma levels and an increase in lag time of conjugated diene formation after the MUFA-diet. There was a positive correlation between the decreases in TFPI and vWF and the changes in total cholesterol, LDL-C, apo B plasma levels. The decrease in TFPI was negatively correlated with the increase in lag time of conjugated diene formation. PAI-1 plasma levels were positively correlated with total cholesterol, LDL-C and triglycerides and negatively correlated with HDL-C. Conclusions : Consumption of a Mediterranean-type MUFA-diet produces a decrease in plasma levels of vWF, TFPI and PAI-1 plasma levels in young healthy males. Given that these substances are of endothelial origin, one could suggest that the MUFA of the diet has a beneficial effect on endothelial function resulting in protective changes against thrombogenesis. © 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Endothelial function; Monounsaturated-rich diet; Plasminogen activator inhibitor type 1; Conjugated diene formation; Plasma lipid profiles www.elsevier.com/locate/atherosclerosis 1. 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 mainte- nance 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 atheroscle- * Corresponding author. Tel.: +34-957-217239; fax: +34-957- 218250. E-mail address: mdipejif@cod.servicom.es (F. Pe ´rez-Jime ´nez) 0021-9150/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved. PII:S0021-9150(99)00116-1