The function of matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP-1) in several clinical conditions: Results and analysis of our survey.

The goal of this research was to evaluate the plasma concentration of MMP-9 and its tissue inhibitor (TIMP-1) in different clinical conditions. It included several groups of subjects: 31 overweight subjects; 91 obese adults divided into two subgroups according to the BMI value (BMI 30-35 Kg/m2 and BMI > 35 Kg/m2); 90 subjects with metabolic syndrome (MS) divided into two subgroups (with and without diabetes mellitus); 100 subjects with preclinical carotid atherosclerosis (PCA) divided according to the number of cardiovascular risk factors and to the insulin resistance degree; 48 subjects with obstructive sleep apnoea syndrome (OSAS) divided according to the apnoea/hypopnea index (AHI); 27 subjects with chronic kidney disease (CKD) on conservative management; 31 subjects with CKD on regular haemodialysis treatment. We have found a significant increase of MMP-9 and TIMP-1 in overweight subjects, in obese adult and in MS subjects. In obese adults, the behaviour of these two parameters was not influenced by the degree of obesity, while in the group of MS subjects both these parameters were clearly influenced by the presence of diabetes mellitus. In subjects with PCA, we observed an increase of MMP-9 associated with a significant decrease of TIMP-1; the same trend was found by subdividing the entire group in accordance with the number of cardiovascular risk factors and with the insulin resistance degree. In subjects with OSAS, we noted an increase in MMP-9 and TIMP-1; this increase was more evident in subjects with OSAS having AHI > 30. In individuals with CKD on conservative and haemodialysis treatment we have found, at baseline, a marked increase in MMP-9 and a significant decrease of TIMP-1. In dialyzed subjects, after a standard dialysis session was noted, a significant increase in MMP-9 was associated with a further decrease in TIMP-1.

Behaviour of carbonyl groups in several clinical conditions: Analysis of our survey.

Protein carbonylation is a marker of oxidative protein damage, that is likely involved in the pathogenesis of several diseases. The aim of this study was to evaluate the protein carbonyl (PC) groups in different clinical conditions. It included different groups of subjects: 81 trained subjects; 23 subjects with mild essential hypertension; 31 middle-aged subjects with metabolic syndrome (MS); 106 subjects with MS not selected for age (subdivided into two subgroups, with and without diabetes mellitus); 91 obese adults subdivided in two subgroups (BMI 30-35 Kg/m2 and BMI > 35 kg/m2); 48 subjects with obstructive sleep apnea syndrome (OSAS) subdivided in accordance with the apnea/hypopnea index (AHI); 27 subjects with chronic kidney disease (CKD) on conservative therapy; 31 subjects with CKD on haemodialysis treatment; and 50 subjects with juvenile myocardial infarction. PC groups were reduced in trained subjects in comparison with sedentary controls, while no variation was observed in mild essential hypertension. PC groups were increased in MS subjects and in adult obese subjects. In MS subjects the PC groups were not influenced by the presence of diabetes mellitus and in adult obese subjects were not influenced by the obesity degree. In OSAS subjects only those with AHI > 30 showed an increase of PC groups. PC groups increased in CKD subjects undergoing conservative treatment and haemodialysis therapy. In dialyzed subjects, after a standard dialysis session, there was a marked increase in PC groups. In juvenile myocardial infarction PC groups were higher than in controls; there was no difference between STEMI and NSTEMI and their concentration was unaffected by the number of cardiovascular risk factors or stenosed coronary vessels.

Plasma Viscosity and NLR in Young Subjects with Myocardial Infarction: Evaluation at the Initial Stage and at 3 and 12 Months.

In the "Sicilian study on juvenile myocardial infarction," we had evaluated plasma viscosity (PV) and neutrophil/lymphocyte ratio (NLR) in patients with acute myocardial infarction (AMI) at the age of ⩽45 years. Now, we examined the relationship between these 2 parameters in 120 subjects (109 men and 11 women) aged ⩽45 years with recent AMI. The patients were classified according to the number of cardiovascular risk factors, the electrocardiographic criteria (ST-segment elevation myocardial infarction [STEMI] or non-ST-segment elevation myocardial infarction [NSTEMI]), and the extent of coronary stenosis, evaluated with coronary angiography. On fasting venous blood, we measured PV at the shear rate of 450 s-1 and NLR. The control group included 50 healthy subjects (mean age = 35.1 ± 7.8 years). At the initial stage, PV and NLR were significantly increased in comparison with controls. Subdividing AMI patients according to the median value of NLR, in the group with high NLR PV was significantly higher, whereas subdividing the patients according to the PV median value, NLR was not different between the 2 groups; 3 and 12 months after AMI, we observed only a significant decrease in NLR. Only PV was discriminant regarding the cardiovascular complications registered during an 18-month follow-up. The evaluation of PV may be of prognostic value in juvenile AMI.

Lipid Peroxidation, Protein Oxidation, Gelatinases, and Their Inhibitors in a Group of Adults with Obesity.

The association between obesity and cardiovascular diseases has a multifactorial pathogenesis, including the synthesis of inflammatory molecules, the increase in oxidative stress and the dysregulation of the matrix metalloprotease (MMP) concentration and activity. In a group of adults with obesity, divided in 2 subgroups according to the body mass index (BMI), we examined lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS), protein oxidation, expressed as protein carbonyl groups (PCs), plasma gelatinases (MMP-2 and MMP-9), and their tissue inhibitors (TIMP-1 and TIMP-2). In the whole group, as well as in the 2 subgroups (with BMI 30-35 or BMI>35) of obese subjects, we observed an increase in TBARS, PCs, MMP-2, and MMP-9, and also TIMP-1 and TIMP-2 in comparison with the control group. A positive correlation between TBARS and PCs emerged in obese subjects and persisted after dividing obese subjects according to BMI. The correlation between MMP-2 and TIMP-2 was not statistically significant, while a significant correlation was present between MMP-9 and TIMP-1. The correlations between the markers of oxidative stress (TBARS and PCs) and those of the MMP/TIMP profile indicated a more marked influence of protein oxidation on MMPs and TIMPs in comparison with TBARS. The innovative aspect of our study was the simultaneous evaluation of oxidative stress markers and MMP/TIMP profile in adult obese subjects. We observed significant alterations and correlations that may negatively influence the clinical course of the disease.

Analysis of the Blood Viscosity Behavior in the Sicilian Study on Juvenile Myocardial Infarction.

Considering the role of hemorheology in coronary circulation, we studied blood viscosity in patients with juvenile myocardial infarction. We examined whole blood viscosity at high shear rate using the cone-on-plate viscosimeter Wells-Brookfield ½ LVT and at low shear rate employing a viscometer Contraves LS30 in 120 patients (aged <46 years) with myocardial infarction, at the initial stage and subsequently 3 and 12 months after. At the initial stage, patients had an increased whole blood viscosity in comparison to normal controls. This hemorheological profile was not influenced by the cardiovascular risk factors, nor by the extent of coronary lesions, even if some differences were evident between patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). The blood viscosity pattern at the initial stage did not influence recurring ischemic events or the onset of heart failure during an 18 months' follow-up. The neutrophil to lymphocyte ratio did not affect the blood viscosity pattern. We reevaluated 83 patients 3 months after and 70 patients 12 months after the acute coronary syndrome, and we found that the hemorheological parameters were still altered in comparison to normal controls at both times. We observed an impairment of the hemorheological pattern in young patients with myocardial infarction, partially influenced by the infarction type (STEMI and NSTEMI) and persisting in the long term.

Red blood cell deformability in multiple myeloma1.

The aim of this study was the evaluation of the erythrocyte deformability in multiple myeloma (MM). We enrolled 29 MM patients and we evaluated, on fasting venous blood, the erythrocyte deformability, expressed as elongation index, and examined using the diffractometric method. By comparing normal controls and MM patients, a significant decrease in erythrocyte deformability, especially at low shear stresses, was found. In this research paper we evaluated all the hypothesis for a possible explanation of the behaviour of red blood cell deformability in MM, even considering how the alteration of erythrocyte deformability worsens the microcirculatory flow in these patients in association with the marked increase in plasma viscosity.

Gelatinases and physical exercise: A systematic review of evidence from human studies.

BACKGROUND: Matrix metalloproteinases (MMPs), particularly gelatinase A (MMP-2) and gelatinase B (MMP-9), as well as their tissue inhibitors (TIMP-1 and TIMP-2), are involved in the development of skeletal muscle tissue, in the repair process after muscle injury and in the adaptive modifications induced by physical exercise in skeletal muscle. This paper aims at reviewing results from human studies that investigated the role of gelatinases and their inhibitors in skeletal muscle response to acute physical exercise or training. METHODS: Electronic databases PubMed/MEDLINE, Scopus and Web of Science were searched for papers published between January 2000 and February 2017. The papers were eligible when reporting human studies in which MMP-2 and/or MMP-9 and/or the inhibitors TIMP-1/TIMP-2 were evaluated, in blood or muscular tissue, before and after acute physical exercise or before and after a period of structured physical training. We included studies on healthy subjects and patients with chronic metabolic diseases (obesity, diabetes mellitus, metabolic syndrome-MS) or asymptomatic coronary artery disease. We excluded studies on patients with neurological, rheumatologic or neoplastic diseases. RESULTS: Studies conducted on muscle biopsies showed an early stimulation of MMP-9 gene transcription as a result of acute exercise, whereas MMP-2 and TIMP transcription resulted from regular repetition of exercise over time. Studies on serum or plasma level of gelatinases and their inhibitors showed an early release of MMP-9 after acute exercise of sufficient intensity, while data on MMP-2 and TIMP were more contrasting. Most of the studies dealing with the effect of training indicated a trend toward reduction in blood gelatinase levels, once again more clear for MMP-9. This result was related to an anti-inflammatory effect of regular exercise and was more evident when training consisted of aerobic activities. This study has limitations: as the initial selection was done through titles and abstracts, incomplete retrieval cannot be excluded, as well as we cannot exclude bias due to selective reporting within studies. CONCLUSION: A better knowledge of the molecular events activated by different types of acute exercise and regular training could be of great relevance in order to maximize the benefits of physical activity in healthy subjects and patients.

Matrix Metalloproteases in Arterial Hypertension and their Trend after Antihypertensive Treatment.

BACKGROUND/AIMS: Arterial hypertension is characterized by vascular remodelling, atherosclerosis and cardiovascular complications. Matrix metalloproteases (MPPs) are endopeptidases produced by all the cells present in the vascular wall and are involved in the regulation of the extracellular matrix protein turnover. MMPs contribute to blood vessel formation, remodelling, angiogenesis; whereas an altered expression or activity of MMPs or their tissue inhibitors (TIMPs) results correlated with the development and progression of cardiovascular complications. METHODS: We examined the literature data regarding the role of MMPs in human hypertension, including their involvement in vascular remodelling, and the effects of some antihypertensive molecules on these MMP/TIMP profile. RESULTS: The expression and the activity of some MMPs and TIMPs are impaired in human hypertension. An altered MMPs/TIMPs balance plays an important role in the vascular wall rearrangement, in response to hemodynamic changes which may induce myocardial hypertrophy and fibrosis leading to ventricular remodelling. Several studies have examined the effects of some antihypertensive molecules, such as ACE inhibitors, angiotensin receptor blockers, calcium-channel blockers, and aldosterone antagonists, on the MMPs/TIMPs profile by obtaining positive results. CONCLUSION: Considering the data taken into consideration, the authors believe that in clinical practice a strategic antihypertensive therapy directed to the MMPs profile, may be useful to decrease the risk of cardiovascular complications.

Clinical conditions responsible for hyperviscosity and skin ulcers complications.

In this brief review, we have examined some clinical conditions that result to be associated to an altered hemorheological profile and at times accompanied by skin ulcers. This skin condition may be observed in patients with the following condtions, such as primary polycythemic hyperviscosity (polycythemia, thrombocytemia) treated with hydroxyurea, primary plasma hyperviscosity (multiple myeloma, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia, and connective tissue diseases), primary sclerocythemic hyperviscosity (hereditary spherocytosis, thalassemia, and sickle cell disease). In addition, it may be present in patients with secondary hyperviscosity conditions such as diabetes mellitus, arterial hypertension, critical limb ischemia and chronic venous insufficiency.

Clinical disorders responsible for plasma hyperviscosity and skin complications.

In this brief review, we have examined some clinical disorders which are associated to an altered hemorheological profile and at times accompanied by skin ulcers. This skin condition may be, in fact, observed in patients with primary plasma hyperviscosity such as multiple myeloma, Waldenstrom macroglobulinemia, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia and connective tissue diseases. It must be underlined that the altered hemorheological pattern is not the only responsible for this skin complication but, as it worsens the microcirculatory flow, it contributes to determine the occurrence of the skin ulcers.

Gelatinases and their tissue inhibitors in a group of subjects with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is associated with an elevated risk of cardiovascular events and stroke. Matrix metalloproteinases (MMPs) are endopeptidases involved in extracellular matrix degradation and then in the development and progression of cardiovascular diseases. Our aim was to evaluate plasma levels of gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in a group of subjects with OSAS. We enrolled 48 subjects (36 men and 12 women; mean age 49.7 ± 14.68 yrs) with OSAS diagnosed with a 1-night cardiorespiratory study and then we subdivided these subjects into two subgroups according to the apnea/hypopnea index (AHI): Low (L = 21 subjects with AHI <30) and High (H = 27 subjects with AHI >30). We measured plasma concentration of the gelatinases and their inhibitors using ELISA kits. We observed a significant increase in plasma concentration of MMP-9, MMP-2, TIMP-1 and TIMP-2 in the entire group of OSAS subjects and in the two subgroups, with higher levels in the H in comparison with the L subgroup. In the whole group of OSAS subjects we also noted a significant decrease in MMP-9/TIMP-1 ratio in comparison with normal controls. Only MMP-9 was significantly correlated with the severity of the disease, expressed as AHI, with the oxygen desaturation index and also with the mean oxygen saturation. MMPs pattern is altered in OSAS and significantly influenced by the severity of the disease; it probably contributes to the vascular remodeling that leads to the atherosclerotic disease and cardiovascular complications.

Obstructive Sleep Apnea Syndrome: Links Betwen Pathophysiology and Cardiovascular Complications.

PURPOSE: The prevalence of obstructive sleep apnea syndrome (OSAS) is increasing, especially in the middle-aged population. OSAS is associated with an elevated risk of cardiovascular morbidity and mortality. Arterial hypertension is often the first consequence of OSAS, but the most severe complications are coronary artery disease, stroke and arrhythmias. The aim of this review was to analyze the several mechanisms involved in the development of the cardiovascular events, such as endothelial dysfunction accompanied by a pro-inflammatory and pro-oxidant status, hemorheological alterations, hypercoagulability and imbalance between matrix metalloproteases and their inhibitors. SOURCE: A search on PubMed was carried out using the following terms: obstructive sleep apnea syndrome; endothelial dysfunction; oxidative stress; inflammation; rheology; matrix metalloproteases. PRINCIPAL FINDINGS: OSAS severity strongly influenced cardiovascular risk factors and, furthermore, it was correlated with the incidence of fatal and non-fatal events. CONCLUSIONS: The treatment with continuous positive airways pressure (cPAP) is the gold standard for OSAS and was able to positively influence all the pathophysiological mechanisms responsible for cardiovascular diseases. Long-term cPAP improved endothelial function and hemorheology, reduced oxidative stress and inflammation, and decreased the levels of metalloproteases.

Lipid peroxidation and nitric oxide metabolites in a group of subjects with obstructive sleep apnea syndrome.

It is known that in OSAS the plasma lipid peroxidation has an opposite behavior in comparison with nitric oxide metabolites. In the re-examination of our survey of OSAS subjects we calculated the ratio between thiobarbituric acid reactive substances (TBARS) and nitric oxide metabolites (NOx) in relation to OSAS severity. The study has regarded 48 OSAS subjects subdivided in two subgroups according to the apnea/hypopnea index - AHI- (Low = 21 subjects with AHI <30 and High = 27 subjects with AHI >30). From the obtained data it is evident that the TBARS/NOx ratio is significantly higher in the H subgroup compared to L subgroup as well as this ratio is reduced in L subgroup in comparison with the whole group of OSAS subjects. In the entire group of OSAS subjects the TBARS/NOx ratio results positively correlated with AHI and ODI and inversely correlated with mSO2.

Nitric oxide metabolites and erythrocyte deformability in a group of subjects with obstructive sleep apnea syndrome.

Our aim was to evaluate nitric oxide metabolites (nitrite and nitrate), expressed as NOx, and erythrocyte deformability, expressed as elongation index, in a group of subjects with obstructive sleep apnea syndrome (OSAS). We enrolled 48 subjects (36 men and 12 women; mean age 50.3±14.68 yrs) with OSAS diagnosed after a 1-night cardiorespiratory sleep study. OSAS severity was assessed evaluating the apnea/hypopnea index (AHI) and subjects were subdivided in two subgroups: Low (L=AHI<30) and High (H=AHI>30). NOx was examined converting nitrate into nitrite with a nitrate reductase and then assessing nitrite with spectrophotometry after the addition of Griess reagent. The elongation index was obtained using the diffractometer Rheodyn SSD of Myrenne at shear stresses of 30 and 60 Pa and it was expressed as elongation index (EI). We found no difference in NOx among the entire group of OSAS subjects and normal controls, while we observed a NOx decrease in the H subgroup in comparison with L subgroup, but not in comparison with normal controls. We noted a significant decrease in EI at each shear stress in the entire group and also in the two subgroups in comparison with controls. The decrease in NO bioavailability and in erythrocyte deformability might contribute to explain the increased cardiovascular risk in OSAS subjects.

Behavior of the total antioxidant status in a group of subjects with metabolic syndrome.

AIMS: Our purpose was to examine the total antioxidant status (TAS) in subjects with metabolic syndrome (MS) subdivided according to the presence or not of diabetes mellitus. METHODS: We enrolled 106 subjects (45 women, 61 men) with MS subsequently subdivided in diabetics (14 women, 29 men) and nondiabetics (31 women, 29 men). TAS was obtained using an Assay kit which relies on the ability of plasma antioxidant substances to inhibit the oxidation of 2,2'-azino-bis(3-ethylbenzthiazoline sulfonic acid) to the radical ABTS·+. RESULTS: In the group of MS subjects a significant decrease in TAS (p<0.05) in comparison with normal controls was evident. This difference was present between normal subjects and nondiabetic subjects with MS (p<0.001) but not between normal and diabetic subjects with MS. Examining the linear regression among TAS, age, anthropometric profile, blood pressure values and glycometabolic pattern, conflicting data were found. CONCLUSIONS: Although we know that TAS includes several enzymatic and non enzymatic antioxidants, we retain that the difference observed in the two subgroups of subjects with MS must be looked in particular into two pathophysiological aspects regarding bilirubin and uric acid.

Lipid peroxidation, nitric oxide metabolites, and their ratio in a group of subjects with metabolic syndrome.

Our aim was to evaluate lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS), nitric oxide metabolites (nitrite + nitrate) expressed as NOx, and TBARS/NOx ratio in a group of subjects with metabolic syndrome (MS). In this regard we enrolled 106 subjects with MS defined according to the IDF criteria, subsequently subdivided into diabetic (DMS) and nondiabetic (NDMS) and also into subjects with a low triglycerides/HDL-cholesterol (TG/HDL-C) index or with a high TG/HDL-C index. In the entire group and in the four subgroups of MS subjects we found an increase in TBARS and NOx levels and a decrease in TBARS/NOx ratio in comparison with normal controls. Regarding all these parameters no statistical difference between DMS and NDMS was evident, but a significant increase in NOx was present in subjects with a high TG/HDL-C index in comparison with those with a low index. In MS subjects we also found a negative correlation between TBARS/NO x ratio and TG/HDL-C index. Considering the hyperactivity of the inducible NO synthase in MS, these data confirm the altered redox and inflammatory status that characterizes the MS and suggest a link between lipid peroxidation, inflammation, and insulin resistance, evaluated as TG/HDL-C index.

Gelatinases and their tissue inhibitors in a group of subjects with metabolic syndrome.

AIM: To evaluate matrix metalloproteases (MMP)-2 and MMP-9 and tissue inhibitor of metalloproteases (TIMP)-1 and TIMP-2 in a group of subjects with metabolic syndrome (MS) subdivided according to the presence or absence of diabetes mellitus. METHODS: We examined in 90 subjects (51 men and 39 women) with MS, defined following the International Diabetes Federation criteria, and subsequently subdivided into diabetic subjects (22 men and 11 women) and nondiabetic subjects s (29 men and 28 women), the plasma concentrations of MMP-2 and MMP-9 and of TIMP-1 and TIMP-2 using specific enzyme-linked immunosorbent assay kits. RESULTS: We found a significant increase in plasma concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 in the whole group of MS subjects (P < 0.001) and in both subgroups of MS subjects with diabetes mellitus (P < 0.001) and without diabetes mellitus (P < 0.001) in comparison with healthy controls. We also noted higher concentrations of all the examined parameters in the MS subjects with diabetes mellitus in comparison with the MS subjects without diabetes mellitus. Matrix metalloproteases and TIMPs showed some significant correlations with body mass index and waist circumference and with metabolic parameters in the whole group of MS subjects. CONCLUSION: An altered pattern of MMPs and their inhibitors is demonstrated in MS; the presence of diabetes mellitus strongly influences the concentration of MMP and TIMP, contributing probably to the increased cardiovascular risk of MS subjects.

Protein oxidation in chronic kidney disease.

An imbalance between oxidative processes and antioxidant systems has been widely demonstrated in chronic kidney diseases (CKD). In this study we enrolled 26 healthy subjects, 27 patients with CKD on conservative treatment (CT-CKD) with various degrees of renal failure, and 31 CKD subjects in haemodialysis treatment (HD-CKD), evaluated before and after a standard haemodialysis session. In each group we measured protein carbonyl groups (PC) as an index of protein oxidation, lipid peroxidation (TBARS) and two plasma markers of leukocyte activation, elastase and myeloperoxidase (MPO). In CT-CKD subjects the PC level was significantly higher than in normal controls, and it was negatively correlated with creatinine clearance. In HD-CKD patients the PC concentration was significantly increased also in comparison with CT-CKD. An increase in TBARS was present both in CT-CKD and in HD-CKD patients, but in HD-CKD patients TBARS were lower than in CT-CKD. Elastase was increased in both CKD groups, while MPO was not different among control and patient groups. In HD-CKD patients the HD session was followed by a further increase in PC, as well as by an increase in elastase and MPO, whereas TBARS did not change. Protein oxidation accelerates the glycation processes and seems to be connected with the chronic inflammatory state detectable in renal failure, although we did not observe any significant correlation between PC level and leukocyte activation markers.

Protein oxidation in a group of subjects with metabolic syndrome.

AIMS: To examine the protein oxidation, marker of the oxidative stress, in metabolic syndrome (MS). METHODS: We enrolled 106 subjects (45 women and 61 men) with MS of which 43 (14 women and 27 men) were with diabetes mellitus and 63 (31 women and 32 men) were without diabetes mellitus, and 54 subjects (19 women and 35 men) as control group. The protein oxidation, expressed as carbonyl groups, was measured by an enzyme-like immunosorbent assay (ELISA) kit (BioCell PC test kit, Enzo Life Sciences AG, Switzerland). RESULTS: In the whole group of MS subjects, in comparison with control group, a significant increase in carbonyl groups was present. The same datum was also evident between control group and diabetic subjects with MS and between control group and nondiabetic subjects with MS. No difference was observed between the two subgroups (diabetic and nondiabetic subjects with MS) about NOx. Few information were obtained examining the linear regression among carbonyl groups, age, BMI, waist circumference, blood pressure values and metabolic pattern of MS subjects. CONCLUSIONS: In MS subject we observed an increase of protein oxidation not influenced by diabetes mellitus. Several strategies may be employed to reduce this parameter.

Protein oxidation in metabolic syndrome.

PURPOSE: Oxidative stress plays a pivotal role in the pathogenesis of the metabolic syndrome and in the progression of its complications. Carbonylated proteins are a stable marker of severe oxidative stress because damage to the protein structure is irreversible and may cause an inhibition of their enzymatic activity or an increased susceptibility to proteolysis. There are few data regarding protein oxidation in metabolic syndrome, although elevated levels of carbonyl groups are often detected in subjects with obesity, diabetes mellitus, hypertension or dyslipidemia, well-known components of the metabolic syndrome. In particular, obesity, insulin resistance and diabetes mellitus are frequently associated with increased protein carbonylation. A relationship between insulin resistance, protein oxidative stress and inflammation has also been suggested as well as protein oxidation products are correlated with overexpression of resistin, TNF-α and IL-6. CONCLUSION: Therapeutic interventions based on lifestyle modifications and pharmacological agents in order to correct all the main risk factors influence oxidative stress and protein carbonylation.