Depressive disorder is an independent risk factor for cardiovascular diseases and is associated with metabolic syndrome (MetS). in women. In conclusion our results suggest that in men high PAI-1 levels are independently associated with long-term mental symptomatology. 1 Introduction An increased prevalence of metabolic syndrome (MetS) is usually a common obtaining among depressed patients . Furthermore depressive disorder is an impartial risk factor for the development of cardiovascular diseases . Nevertheless causal associations between these factors remain unclear  although several behavioral or physiological mechanisms have been suggested . According to previous studies increased serum plasminogen activator inhibitor-1 (PAI-1) levels are associated Ambrisentan with Rabbit Polyclonal to SEPT1. metabolic changes  and possibly also with mental health problems . Furthermore depressive disorder is a significant public health care issue worldwide and the incidence of metabolic syndrome is increasing drastically. The relationship between these two conditions is usually bidirectional . Nevertheless the factors regulating these associations are unclear. Plasminogen activator inhibitor-1 (PAI-1) is usually a major physiological inhibitor of tissue-type (tPA) and urokinase-type plasminogen (uPA) activators. It also possesses several other functions in human physiology. PAI-1 belongs Ambrisentan to the family of serine protease inhibitors (SERPINs) and it is an inhibitor of intravascular fibrinolysis and cell-associated proteolysis. Under Ambrisentan normal physiological conditions PAI-1 is usually synthesized by the liver easy muscle cells adipocytes and platelets . However in pathological conditions such as atherosclerosis endothelial cells and other inflammatory-stimulated cells secrete notable amounts of PAI-1 . In addition abdominal obesity is related to elevated PAI-1 plasma concentrations and thus increased amounts of adipose tissue might contribute to PAI-1 secretion especially in obese subjects . Circulating PAI-1 is found in two conformationally distinct forms: an active form which has a relatively short plasma half-life (~30 min) and a latent inactive form . Binding to a carrier protein Ambrisentan vitronectin stabilizes the active form of PAI-1 . PAI-1 is also found in cerebrospinal fluid . tPA can cross the blood-brain barrier (BBB)  and is synthesized in several brain regions . Furthermore Yepes et al. reported that tPA increased BBB permeability after ischemic stroke . Whether PAI-1 itself is usually capable of crossing the BBB is currently unknown. However Hino et al. showed immunohistochemically the localization of type 1 plasminogen activator inhibitor in human brain tissues . Recent findings suggest a link between elevated PAI-1 levels and major depressive disorder (MDD) [17 18 However the role of metabolic syndrome was not assessed in these studies. As PAI-1 is an impartial and true component of metabolic syndrome we examined the additional effect of mental symptoms around the previously observed association between metabolic syndrome and PAI-1. Moreover the possible gender differences have not been resolved in previous studies. Thus in the present study we examined the role of long-term adverse mental symptoms (LMS) in subjects with metabolic syndrome in the regulation of PAI-1 levels in a population-based sample of both men and women. 2 Methods 2.1 Study Population The present study was a part of the longitudinal population-based Kuopio Depressive disorder Study (KUDEP) in the central-eastern a part of Finland [1 19 20 The random general population sample (= 3004) was initially selected from the National Populace Register in 1998. Study questionnaires were mailed to the subjects. The baseline sample consisted of 2050 respondents aged 25-65 years. Follow-ups were performed Ambrisentan in 1999 (= 1722) and in 2001 (= 1593). Altogether 1347 subjects responded three times. The sample of the present study was from subgroups of this 3-12 months followup study. The inclusion criteria for the sample were based on the presence or absence of self-reported mental symptoms prevailing at baseline and at both follow-ups. First we selected subjects Ambrisentan who reported at least one of the following at each followup: high Beck Depressive disorder.