Gender-Associated Biomarkers in Metabolic Syndrome

Metabolic syndrome (MetS) is a cluster of risk factors for atherosclerosis, including abdominal obesity, hypertension, insulin resistance, dyslipidemia with high triglycerides, and low high-density lipoprotein cholesterol. Affected patients have a significantly increased risk of developing cardiovascular disorders (CVD), that are the leading cause of death in the Western countries. Several epidemiological studies have investigated the evolution of CVD hypothesizing the presence of a gender difference in the pathogenetic and progression determinants detectable in men and women. In this chapter, we will examine new gender-associated bioindicators of possible diagnostic or prognostic value in the MetS. Moreover, we will provide an overview on current knowledge on sex-associated cardiovascular determinants with the aim to improve CVD diagnostic and prognostic clinical courses and to develop new and gender-biased prevention strategies

Oxidative stress in the pathogenesis of systemic scleroderma: An overview

Systemic sclerosis (SSc) is a rare disorder of the connective tissue characterized by fibrosis of the skin, skeletal muscles and visceral organs. Additional manifestations include activation of the immune system and vascular injury. SSc causes disability and death as the result of end-stage organ failure. Two clinical subsets of the SSc are accepted: limited cutaneous SSc (lc-SSc) and diffuse cutaneous SSc (dc-SSc). At present, the aetiology and pathogenesis of SSc remain obscure, and consequently, disease outcome is unpredictable. Numerous studies suggest that reactive oxidizing species (ROS) play an important role in the pathogenesis of scleroderma. Over the years, several reports have supported this hypothesis for both lc-SSc and dc-SSc, although the specific role of oxidative stress in the pathogenesis of vascular injury and fibrosis remains to be clarified. The aim of the present review was to report and comment the recent findings regarding the involvement and role of oxidative stress in SSc pathogenesis. Biomarkers proving the link between ROS and the main pathological features of SSc have been summarized

Possible Implication of Red Blood Cells in the Prothrombotic Risk in Early Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that can be considered as a prothrombotic state1. A great number of studies have investigated the possible role of reactive oxygen species (ROS) in the etiology and pathogenesis of this disease. The presence of large amounts of superoxide radicals and hydrogen peroxide produced by activated neutrophils has been reported in the synovial fluid of patients with RA. This may cause lipid peroxidation that yields a wide variety of end products, including malondialdehyde (MDA), a known marker of oxidative stress. These products are therefore transported from the synovial fluid to the blood circulation system2. Considering that elevated levels of MDA have been observed in the blood plasma of patients with RA2, the aim of this pilot study was to investigate whether the elevated levels of plasmatic MDA could be associated with a modification of the total antioxidant capacity (TAC) of blood plasma that is usually indicative of a “systemic” oxidative imbalance3. In addition, in view of their activity as redox effectors or scavengers4, as well as determinants of thrombus formation5, we evaluated red blood cell (RBC) features in terms of their redox state and lifespan marker molecules

On the interference of sildenafil on platelet aggregation: An ex vivo pilot study

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Single exposure of human fibroblasts (WI-38) to a sub-cytotoxic dose of UVB induces premature senescence

AbstractIn this work, we present a new model of stress-induced premature senescence obtained by exposing human fibroblasts (WI-38) at early passages (passages 2–4) to a single sub-cytotoxic dose of UVB (200mJ/cm2). We show that this treatment leads to the appearance of several biomarkers of senescence such as enlarged and flattened cell morphology, the presence of nuclear heterochromatic foci and β-galactosidase activity. Furthermore, we demonstrate that a mild ROS production and p53 activation are upstream events required for the induction of premature senescence. Our method represents an alternative in vitro model in photoaging research and could be used to test potential anti-photoaging compounds

The Red Blood Cell as a Gender-Associated Biomarker in Metabolic Syndrome: A Pilot Study

In the present pilot study (56 patients), some red blood cell parameters in samples from patients with metabolic syndrome and subclinical atherosclerosis, but without any sign of coronary artery disease, have been analyzed. The main goal of this work was to determine, in this preclinical state, new peripheral gender-associated bioindicators of possible diagnostic or prognostic value. In particular, three different “indicators” of red blood cell injury and aging have been evaluated: glycophorin A, CD47, and phosphatidylserine externalization. Interestingly, all these determinants appeared significantly modified and displayed gender differences. These findings could provide novel and useful hints in the research for gender-based real-time bioindicators in the progression of metabolic syndrome towards coronary artery disease. Further, more extensive studies are, however, necessary in order to validate these findings

Functional Estrogen Receptors of Red Blood Cells. Do They Influence Intracellular Signaling?

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Sex-related biomarkers in cardiovascular and neurodegenerative disorders

Despite considerable advances in the treatment of human inflammatory diseases, such as cardiovascular and neurological disorders, they remain the leading cause of death in developed countries. From a clinical perspective, an active area of investigation focuses on the identification of diagnostic and prognostic biomarkers, because preventing events in those at risk of chronic inflammatory disease is likely to have a substantial impact on the overall public-health burden. The sex difference has not been considered previously as important in the evaluation of biomarkers of human diseases, twithstanding it is now ascertained that the severity of these disorders is correlated with sex hormones which modulate the inflammatory response. The aim of the present brief review is to report and comment the state of art regarding the sex-related biomarkers in cardiovascular and neurodegenerative disorders, focusing on those compounds showing potential prognosticand diagnostic values, and/or acting as indicators of the therapeutic treatment efficacy