Plasminogen Activator Inhibitor-1 and Relations to Fatty Acid Composition in the Diet and in Serum Cholesterol Esters

Abstract

Abstract-High plasminogen activator inhibitor (PAI)-1 levels and poor dietary fat quality are potential risk factors for cardiovascular disease. The aim was to investigate the cross-sectional associations between PAI-1 activity and dietary nutrient intake, focusing on fat quality, in a population-based study of 871 men aged 70 years. The relationship between PAI-1 and the fatty acid composition in serum cholesterol esters (nϭ381 men) was also studied. The estimated total fat intake was positively associated with PAI-1 activity. The intake of both monounsaturated and polyunsaturated fatty acids was positively associated with PAI-1 activity, whereas the intake of saturated fatty acids was not. In serum cholesterol esters, higher proportions of palmitoleic and dihomo-␥-linolenic acid, a lower proportion of linoleic acid, and reduced estimated ⌬5-desaturase activity were associated with higher PAI-1 levels. These associations were confounded by factors representing the insulin resistance syndrome. PAI-1 activity was positively associated with ␥-linolenic and arachidonic acid, independent of potential confounders. In conclusion, this study demonstrates that dietary intake of unsaturated fatty acids is positively associated with PAI-1 activity, whereas intake of saturated fatty acids is not. The associations present between PAI-1 activity and the fatty acid proportions in serum cholesterol esters are partly influenced by metabolic syndrome-related factors. Key Words: plasminogen activator inhibitor-1 Ⅲ fatty acid composition Ⅲ diet Ⅲ serum cholesterol esters Ⅲ population-based study I schemic heart disease and cerebrovascular disease are the 2 leading causes of death in the industrialized world. 1 The role of dietary fat quality in cardiovascular disease is under due investigation. It has been suggested that unsaturated fatty acids reduce the risk of cardiovascular disease, whereas saturated fatty acids seem to be deleterious. 2 Also, the role of coagulation and fibrinolytic factors in cardiovascular disease is discussed. In many conditions involving an increased risk of cardiovascular disease, such as type II diabetes and glucose intolerance, there is a tendency to hypercoagulation, hypofibrinolysis, or a combination of both. A high level of plasminogen activator inhibitor (PAI)-1, the main regulator of the fibrinolytic system, has been suggested as one of the important factors involved in the genesis of atherothrombosis in conditions involving a high risk of cardiovascular disease. 3 The regulation of PAI-1 levels includes genetic and environmental factors. 3 Possible important environmental factors that vary along with PAI-1 are as follows: central obesity; concentrations of plasma insulin, proinsulin, and triglyceriderich lipoprotein particles; and dietary habits. Observational studies have demonstrated inverse associations between PAI-1 levels and the intake of carbohydrates 4 and of fibers. 4,5 The intake of fat 4 and alcohol consumption 6,7 were positively associated with PAI-1. Studies investigating the effect...

Factor analysis of fatty acids in serum lipids as a measure of dietary fat quality in relation to the metabolic syndrome in men

“…FAs of the nҀ3 family are generally regarded as being protective against cardiovascular disease (28,29), which is supported by our results, ie, a higher nҀ3 PUFA factor (factor 3) score was negatively associated with MetS. D5D activity in skeletal muscle membranes was previously shown to be associated with better insulin sensitivity (30,31), and previous studies in the ULSAM cohort showed that low D5D activity independently predicts MI (15) and that D5D activity is negatively associated with plasminogen activator inhibitor 1 (32). The positive loading from ⌬9 -18 in factor 3 ( Table 2) might seem surprising, because high SCD-1 activity is associated with insulin resistance.…”

Fatty acid composition of serum lipids predicts the development of the metabolic syndrome in men

“…Low estimated D5D activity significantly predicted the development of metabolic syndrome in the present study, independently of lifestyle factors (smoking, physical activity and BMI) assessed at baseline, as well as the estimated activity of SCD-1 and D6D. Previous studies have reported decreased estimated D5D activity as an independent risk factor for myocardial infarction [24], and Byberg and colleagues found estimated D5D activity to be negatively associated with PAI-1 activity [27]. Our data might indicate that low estimated D5D activity is an early sign of the risk of developing metabolic syndrome, which 20 years later results in manifest metabolic syndrome.…”

Influence of diet on atherogenic risk in children with renal transplants

“…In this same group of transplanted patients we found that plasma PAI-1 activity was significantly elevated and correlated positively with CRP, fasting insulinemia, and the HOMA index [4]. The finding in the present study of an association between plasma PAI-1 activity and total fat intake was expected [33]. The negative correlation between plasma PAI-1 activity and intake of saturated fatty acids is difficult to explain but may also be related to the diet, which included a smaller proportion of saturated than unsaturated fatty acids.…”

“…The negative correlation between plasma PAI-1 activity and intake of saturated fatty acids is difficult to explain but may also be related to the diet, which included a smaller proportion of saturated than unsaturated fatty acids. However, and probably as a consequence of the sample size, we could not find the positive correlation reported between intake of unsaturated fatty acids and plasma PAI-1 activity [33]. This thrombogenic effect of unsaturated fatty acids, if it really exists, is apparently paradoxical since it is widely believed that a high intake of unsaturated fatty acids protects against atherogenesis.…”