Depressive disorder is an independent risk factor for cardiovascular diseases and

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 [1]. Furthermore depressive disorder is an impartial risk factor for the development of cardiovascular diseases [2]. Nevertheless causal associations between these factors remain unclear [3] although several behavioral or physiological mechanisms have been suggested [4]. According to previous studies increased serum plasminogen activator inhibitor-1 (PAI-1) levels are associated Ambrisentan with Rabbit Polyclonal to SEPT1. metabolic changes [5] and possibly also with mental health problems [6]. 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 [7]. 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 [8]. However in pathological conditions such as atherosclerosis endothelial cells and other inflammatory-stimulated cells secrete notable amounts of PAI-1 [8]. 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 [9]. 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 [10]. Binding to a carrier protein Ambrisentan vitronectin stabilizes the active form of PAI-1 [11]. PAI-1 is also found in cerebrospinal fluid [12]. tPA can cross the blood-brain barrier (BBB) [13] and is synthesized in several brain regions [14]. Furthermore Yepes et al. reported that tPA increased BBB permeability after ischemic stroke [15]. 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 [16]. 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.