Abstract
Metabolic Syndrome (MetS) has become a worldwide epidemic, alongside with a high socioeconomic cost, and its diagnostic criteria must include at least three out of the five features: visceral obesity, hypertension, dyslipidemia, insulin resistance, and high fasting glucose levels. MetS shows an increased oxidative stress associated with platelet hyperactivation, an essential component for thrombus formation and ischemic events in MetS patients. Platelet aggregation is governed by the peroxide tone and the activity of Protein Disulfide Isomerase (PDI) at the cell membrane. PDI redox active sites present active cysteine residues that can be susceptible to changes in plasma oxidative state, as observed in MetS. However, there is a lack of knowledge about the relationship between PDI and platelet hyperactivation under MetS and its metabolic features, in spite of PDI being a mediator of important pathways implicated in MetS-induced platelet hyperactivation, such as insulin resistance and nitric oxide dysfunction. Thus, the aim of this review is to analyze data available in the literature as an attempt to support a possible role for PDI in MetS-induced platelet hyperactivation.
Highlights
Definition of Metabolic Syndrome (MetS) has been a matter of intense scientific output over the last decades, reaching a consensus by The National Cholesterol Education Program– Adult Treatment Panel (NCEP ATP III) to include five major features: visceral obesity, hypertension, dyslipidemia, insulin resistance, and high fasting glucose levels
The prothrombotic state in MetS is mainly caused by endothelial dysfunction and platelet hyperactivity. Both lipotoxicity and insulin resistance contribute to increased oxidative stress (OxS) in the endothelium, leading to enhanced production of reactive oxygen species (ROS) by various isoforms of NADPH oxidase (Nox) and reduced nitric oxide (NO) production and bioavailability, consequent to lower expression and/or uncoupling of endothelial nitric oxide synthase as well as increased reactivity with superoxide (O2∙−) [8]
Since MetS involves many risk factors associated to changes in the coagulation pathway, the aim of this review is to analyze the potential role of platelet surface PDIA1, referred as Protein Disulfide Isomerase (PDI), as a central player in platelet hyperactivation under MetS
Summary
Definition of Metabolic Syndrome (MetS) has been a matter of intense scientific output over the last decades, reaching a consensus by The National Cholesterol Education Program– Adult Treatment Panel (NCEP ATP III) to include five major features: visceral obesity, hypertension, dyslipidemia, insulin resistance, and high fasting glucose levels. The prothrombotic state in MetS is mainly caused by endothelial dysfunction and platelet hyperactivity. Both lipotoxicity and insulin resistance contribute to increased oxidative stress (OxS) in the endothelium, leading to enhanced production of reactive oxygen species (ROS) by various isoforms of NADPH oxidase (Nox) and reduced nitric oxide (NO) production and bioavailability, consequent to lower expression and/or uncoupling of endothelial nitric oxide synthase (eNOS) as well as increased reactivity with superoxide (O2∙−) [8]. There is an increase in prothrombotic factors with a concomitant decrease in inhibitory components in both endothelium and platelets that concur for increased CVD in MetS. Since MetS involves many risk factors associated to changes in the coagulation pathway, the aim of this review is to analyze the potential role of platelet surface PDIA1, referred as PDI, as a central player in platelet hyperactivation under MetS
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