Melatonin suppresses atherosclerosis by ferroptosis inhibition via activating NRF2 pathway.

Melatonin (MLT), a conserved small indole compound, exhibits anti-inflammatory and antioxidant properties, contributing to its cardioprotective effects. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with atherosclerosis disease risk, and is known as an atherosclerosis risk biomarker. This study aimed to investigate the impact of MLT on Lp-PLA2 expression in the atherosclerotic process and explore the underlying mechanisms involved. In vivo, ApoE-/- mice were fed a high-fat diet, with or without MLT administration, after which the plaque area and collagen content were assessed. Macrophages were pretreated with MLT combined with ox-LDL, and the levels of ferroptosis-related proteins, NRF2 activation, mitochondrial function, and oxidative stress were measured. MLT administration significantly attenuated atherosclerotic plaque progression, as evidenced by decreased plaque area and increased collagen. Compared with those in the high-fat diet (HD) group, the levels of glutathione peroxidase 4 (GPX4) and SLC7A11 (xCT, a cystine/glutamate transporter) in atherosclerotic root macrophages were significantly increased in the MLT group. In vitro, MLT activated the nuclear factor-E2-related Factor 2 (NRF2)/SLC7A11/GPX4 signaling pathway, enhancing antioxidant capacity while reducing lipid peroxidation and suppressing Lp-PLA2 expression in macrophages. Moreover, MLT reversed ox-LDL-induced ferroptosis, through the use of ferrostatin-1 (a ferroptosis inhibitor) and/or erastin (a ferroptosis activator). Furthermore, the protective effects of MLT on Lp-PLA2 expression, antioxidant capacity, lipid peroxidation, and ferroptosis were decreased in ML385 (a specific NRF2 inhibitor)-treated macrophages and in AAV-sh-NRF2 treated ApoE-/- mice. MLT suppresses Lp-PLA2 expression and atherosclerosis processes by inhibiting macrophage ferroptosis and partially activating the NRF2 pathway.

Association of lipoprotein-associated phospholipase A2 mass with asymptomatic cerebral artery stenosis.

Cerebral artery stenosis (CAS) is the most important causes of ischaemic stroke. Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays 2 diverse roles in atherosclerosis (pro-inflammatory and anti-inflammatory), and the association between Lp-PLA2 mass and cardiovascular or cerebrovascular events is inconsistent among previous studies. A cross-sectional study including 2012 North Chinese adults aged ≥40 years was performed in 2010-2011 to investigate whether Lp-PLA2 mass is associated with asymptomatic cerebral artery stenosis (ACAS). Serum Lp-PLA2 mass was determined by enzyme-linked immunosorbent assay (ELISA). All participants underwent transcranial Doppler (TCD) and bilateral carotid duplex ultrasound to evaluate intracranial artery stenosis (ICAS) and extracranial arterial stenosis (ECAS). The median serum Lp-PLA2 mass of the participants was 140.74 ng/mL (interquartile range: 131.79-158.07 ng/mL). The adjusted odds ratio (OR) when comparing the 4th quartile to the 1st quartile of Lp-PLA2 was 1.98 (95% confidence interval (CI): 1.42-2.78), 1.79 (95% CI: 1.08-2.94) and 1.87 (95% CI: 1.28-2.73) for the occurrence of ACAS, asymptomatic ECAS and asymptomatic ICAS, respectively, after controlling for vascular risk factors. These independently significant associations remained statistically significant in the male or elderly subgroups, but not in females or middle-aged participants. Lp-PLA2 mass is positively correlated with subclinical atherosclerosis determined by ACAS, ICAS and ECAS in North Chinese, particularly in male and older participants, suggesting that serum Lp-PLA2 mass might be potential biomarker for the detection of ACAS in the adults.

[Lp-PLA2, a biomarker of vascular inflammation and vulnerability of atherosclerosis plaques]. / La Lp-PLA2, marqueur d'inflammation vasculaire et de vulnérabilité de la plaque d'athérosclérose.

A chronic inflammation is involved in various stages of development of the atherosclerotic plaques. Among the emerging biomarkers of atherogenesis, the lipoprotein-associated phospholipase A2 (Lp-PLA2), formerly known as PAF-acetylhydrolase (McIntyre et al., 2009), hydrolyses the oxidized short chain phospholipids of low-density lipoproteins (LDL), thereby releasing pro-inflammatory mediators (lysophospholipids and oxidized fatty acids). Lp-PLA2, produced by monocytes/macrophages and T-lymphocytes, and mainly associated with LDL (Gazi et al., 2005), is predominantly expressed in the necrotic center of the atherosclerotic plaques and in the macrophage-rich areas (Kolodgie et al., 2006). It would have a predictive role of cardiovascular (CV) events in relation to the vulnerability of atherosclerotic plaques. Determination of Lp-PLA2 has been proposed in the assessment of the CV risk, to ensure a better stratification of populations at intermediate risk for targeted therapy (Davidson et al., 2008). Its proatherogenic role suggested that inhibition of its activity could ensure a better vascular protection in combination with cholesterol-lowering agents. Nevertheless, Lp-PLA2 is not yet a fully validated marker for use in daily clinical practice, especially since the studies using an inhibitor of Lp-PLA2 (darapladib) (STABILITY Investigators et al., 2014; O'Donoghue et al., 2014) did not show any reduction in coronary events. Lp-PLA2 could have a site-specific role in plaque inflammation and development (Fenning et al., 2015). High Lp-PLA2 activity could reflect a response to pro-inflammatory stress characteristic of atherosclerosis (Marathe et al., 2014). This presentation aims at clarifying the involvement of Lp-PLA2 in the pathophysiology of atherosclerosis, and at assessing its interest both as a biomarker for the onset of CV events and as a therapeutic target.

Lipoprotein-Associated Phospholipase A2: A Novel Contributor in Sjögren's Syndrome-Related Lymphoma?

Background: B-cell non-Hodgkin's lymphoma (B-NHL) is one of the major complications of primary Sjögren's syndrome (SS). Chronic inflammation and macrophages in SS minor salivary glands have been previously suggested as significant predictors for lymphoma development among SS patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2)-a product mainly of tissue macrophages-is found in the circulation associated with lipoproteins and has been previously involved in cardiovascular, autoimmune, and malignant diseases, including lymphoma. Objective: The purpose of the current study was to investigate the contributory role of Lp-PLA2 in B-NHL development in the setting of primary SS. Methods: Lp-PLA2 activity in serum samples collected from 50 primary SS patients with no lymphoma (SS-nL), 9 primary SS patients with lymphoma (SS-L), and 42 healthy controls (HC) was determined by detection of [3H]PAF degradation products by liquid scintillation counter. Moreover, additional sera from 50 SS-nL, 28 SS-L, and 32 HC were tested for Lp-PLA2 activity using a commercially available ELISA kit. Lp-PLA2 mRNA, and protein expression in minor salivary gland (MSG) tissue samples derived from SS-nL, SS-L patients, and sicca controls (SC) were analyzed by real-time PCR, Western blot, and immunohistochemistry. Results: Serum Lp-PLA2 activity was significantly increased in SS-L compared to both SS-nL and HC by two independent methods implemented [mean ± SD (nmol/min/ml): 62.0 ± 13.4 vs 47.6 ± 14.4 vs 50.7 ± 16.6, p-values: 0.003 and 0.04, respectively, and 19.4 ± 4.5 vs 15.2 ± 3.3 vs 14.5 ± 3.0, p-values: <0.0001, in both comparisons]. ROC analysis revealed that the serum Lp-PLA2 activity measured either by radioimmunoassay or ELISA has the potential to distinguish between SS-L and SS-nL patients (area under the curve [AUC]: 0.8022, CI [95%]: 0.64-0.96, p-value: 0.004 for radioimmunoassay, and AUC: 0.7696, CI [95%]: 0.66-0.88, p-value: <0.0001, for ELISA). Lp-PLA2 expression in MSG tissues was also increased in SS-L compared to SS-nL and SC at both mRNA and protein level. ROC analysis revealed that both MSG mRNA and protein Lp-PLA2 have the potential to distinguish between SS-nL and SS-L patients (area under the curve [AUC] values of 0.8490, CI [95%]: 0.71-0.99, p-value: 0.0019 and 0.9444, CI [95%]: 0.79-1.00, p- value: 0.0389 respectively). No significant difference in either serum Lp-PLA2 activity or MSG tissue expression was observed between SS-nL and HC. Conclusions: Lp-PLA2 serum activity and MSG tissue mRNA/protein expression could be a new biomarker and possibly a novel therapeutic target for B-cell lymphoproliferation in the setting of SS.

On the present and future role of Lp-PLA2 in atherosclerosis-related cardiovascular risk prediction and management.

Circulating concentration and activity of secretory phospholipase A2 (sPLA2) and lipoprotein-associated phospholipase A2 (Lp-PLA2) have been proven as biomarkers of increased risk of atherosclerosis-related cardiovascular disease (ASCVD). Lp-PLA2 might be part of the atherosclerotic process and may contribute to plaque destabilisation through inflammatory activity within atherosclerotic lesions. However, all attempts to translate the inhibition of phospholipase into clinically beneficial ASCVD risk reduction, including in randomised studies, by either non-specific inhibition of sPLA2 (by varespladib) or specific Lp-PLA2 inhibition by darapladib, unexpectedly failed. This gives us a strong imperative to continue research aimed at a better understanding of how Lp-PLA2 and sPLA2 regulate vascular inflammation and atherosclerotic plaque development. From the clinical viewpoint there is a need to establish and validate the existing and emerging novel anti-inflammatory therapeutic strategies to fight against ASCVD development, by using potentially better animal models and differently designed clinical trials in humans.

Carotid Plaque Inflammation Assessed by 18F-FDG PET/CT and Lp-PLA2 Is Higher in Symptomatic Patients.

Carotid plaque inflammation assessed by 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are higher in symptomatic patients. The aim of this study was to assess correlations between 18F-FDG uptake on PET scan of carotid artery plaques, plasma levels of Lp-PLA2, and cerebrovascular symptoms. The study included 45 consecutive patients (22 symptomatic, 23 asymptomatic) with >70% carotid stenosis. Patients were examined by hybrid PET/CT, and maximum standardized uptake values (SUVmax) were recorded. Blood samples were obtained, and plasma was stored at -80 °C for subsequent Lp-PLA2 analysis. Symptomatic and asymptomatic patients showed no significant difference in classical cardiovascular risk factors. Asymptomatic carotid stenosis patients more frequently had a history of coronary artery disease (P = .025) and peripheral artery disease (P = .012). The symptomatic group had higher 18F-FDG uptake in carotid plaques (P < .001), higher plasma Lp-PLA2 (P < .01), and higher high-sensitive C-reactive protein (P = .022). 2-Deoxy-2-[18F]fluoro-D-glucose uptake on PET/CT and plasma Lp-PLA2 show a statistically significant association with the symptomatic status of carotid plaques.

Association of PAF and its Metabolic Enzymes with GGT and the Fatty Liver Index in Healthy Volunteers.

BACKGROUND: Platelet-activating-factor (PAF) is a lipid inflammatory mediator implicated in liver disease. Its main biosynthetic enzymes are cytidine diphosphate (CDP)-choline: 1-alkyl-2-acetyl-sn-glycerol-cholinephosphotransferase (PAF-CPT) and acetyl-coenzyme A: lyso-PAF-acetyltransferases (Lyso-PAF-AT). At the same time, PAF acetylhydrolase (PAF-AH) and lipoprotein-associated phospholipase A2 (Lp-PLA2 ) degrade PAF. OBJECTIVE: To explore the relation of PAF metabolism with liver diseases and non-alcoholic fatty liver disease, as reflected by the fatty liver index (FLI). METHODS: In 106 healthy volunteers, PAF concentration, the activity of its metabolic enzymes and gamma-glutamyl transferase (GGT) were measured in whole blood, leukocytes and serum, respectively and the FLI was calculated. Partial correlations and linear regression models were used. RESULTS: In males, serum GGT activity was positively correlated with abdominal fat (as assessed by analysis of a manually defined region of interest in dual-energy X-ray absorptiometry), triacylglycerols, bound-PAF and Lp-PLA2 , while the FLI was positively correlated with Lp-PLA2 activity. In females, serum GGT activity was negatively associated with high-density lipoprotein cholesterol (HDL-C) (age adjusted correlations, all p<0.05). Lp-PLA2 was a significant determinant of serum GGT activity in males after controlling for age, low- density lipoprotein cholesterol (LDL-C) and abdominal fat. The addition of bound-PAF in the model significantly increased the explained variance of serum GGT activity (total variance explanation 30%). CONCLUSION: Bound-PAF and Lp-PLA2 activity predicted serum GGT activity while Lp-PLA2 was also related to FLI. Our findings shed light on the metabolic pathways linking Lp-PLA2 to other atherosclerosis and/or oxidative markers, such as HDL-C, LDL-C, GGT and FLI and underline the important role of PAF.

Impact of tyrosine nitration at positions Tyr307 and Tyr335 on structural dynamics of Lipoprotein-associated phospholipase A2-A therapeutically important cardiovascular biomarker for atherosclerosis.

Protein tyrosine nitration (PTN) is a post translational event which results in the generation of 3-Nitrotyrosine (3-NT). High levels of 3-NT were reported in several human diseases such as Parkinson's disease, Alzheimer's disease, amylotrophic lateral sclerosis and coronary artery disease. It was reported that PTN at positions 307 and 335 of Lipoprotein-associated phospholipase A2 (Lp-PLA2) curtails its enzymatic activity but the mechanism of inhibition at the structure level is still incomprehensible. The present study is an in silico endeavor to understand nitrative stress induced structural changes in Lp-PLA2. Molecular docking studies revealed a decreased binding affinity of substrate, Platelet Activating Factor (PAF) with the nitrated forms of Lp-PLA2 (NT-Tyr307 and NT-Tyr335) compared to the wild type, due to differences in the hydrogen bond interaction patterns. Molecular dynamics (MD) simulation studies suggests higher flexibility of nitrated forms compared to wild type, disorientation of the catalytic triad and decreased molecular interactions of NT-Tyr307 and NT-Tyr335 with other residues of the protein. Essential dynamics (ED) further confirmed the enhanced structural flexibility of nitrated forms of Lp-PLA2. Our findings would help understand the molecular mechanism of nitrative stress induced inhibition of Lp-PLA2 which may further assist in designing of therapeutics having protective functions against PTN.

Endothelial function after ST-elevation myocardial infarction in patients with high levels of high-sensitivity CRP and Lp-PLA2: A substudy of the RESPONSE randomized trial.

BACKGROUND: The combination of high levels of high-sensitive C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase-A2 (Lp-PLA2) was recently shown to correlate with increased cardiovascular risk. Endothelial dysfunction is also known to be a risk factor for cardiovascular events. AIM: To test among patients with previous ST-elevation myocardial infarction (STEMI) the hypothesis that high levels of both hs-CRP and Lp-PLA2 may be associated with impaired endothelium-dependent vasodilatation. METHODS: In this substudy of the RESPONSE randomized trial, we used reactive hyperemia peripheral artery tonometry (RH-PAT) 4 to 6weeks after STEMI and primary percutaneous coronary intervention (PPCI) to non-invasively assess endothelial function (RH-PAT index <1.67 identified endothelial dysfunction). Reliable measurements of RH-PAT, hs-CRP, and Lp-PLA2 were obtained in 68 patients, who were classified as high-risk if levels of both hs-CRP and Lp-PLA2 were in the upper tertile (≥3.84mg/L and >239µg/L, respectively). RESULTS: Patients were 57.4±9.7years and 53 (77.9%) were men. 11 (16%) patients were classified as high-risk and 57 (84%) as low-to-intermediate-risk. The RH-PAT index was 1.68±0.22 in high-risk and 1.95±0.63 in low-to-intermediate-risk patients (p=0.17). Endothelial dysfunction was present in 8 (72.7%) high-risk and 26 (45.6%) low-to-intermediate-risk patients (p=0.09). Framingham risk score, NT-proBNP and fibrinogen levels were higher in high-risk patients (p≤0.03). CONCLUSION: In this population of patients with recent STEMI and PPCI, we observed between patients with high hs-CRP and Lp-PLA levels and all other patients no more than numerical differences in endothelial function that did not reach a statistical significance. Nevertheless, further research in larger study populations may be warranted.

Adipocyte fatty acid binding protein levels in patients with coronary artery disease and its relationship to alternative biomarkers.

BACKGROUND AND AIM: An association between circulating adipocyte fatty acid-binding protein (A-FABP) levels and coronary artery disease (CAD) has been reported. In this case-control study, we investigated the relationship between plasma levels of A-FABP and the severity of CAD in Turkish subjects. We also assessed its relationship to alternative biomarkers. METHODS: Two hundred and eighty patients undergoing coronary angiography were enrolled in the study. By means of coronary angiography, the study population was divided into subjects without any angiographically detectable CAD (no vessel disease; n = 88) and individuals with single-vessel disease (n = 65), or double- or triple-vessel disease (n = 127). Lipid concentrations were measured by an autoanalyser and A-FABP, lipoprotein associated phospholipase A2 (Lp-PLA2), oxidised-low density lipoprotein (ox-LDL) and high-sensitivity C-reactive protein (hsCRP) levels by a commercial enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: In our study population, total cholesterol and LDL cholesterol levels did not differ significantly between the groups. Levels of high density lipoprotein cholesterol, A-FABP, Lp-PLA2, ox-LDL and hsCRP were significantly different among groups. The higher levels of A-FABP, Lp-PLA2, ox-LDL and hsCRP levels were shown in patients with double/triple-vessel disease. There was not a significant correlation between A-FABP and other biomarkers in CAD patients. CONCLUSIONS: Initially, plasma levels of A-FABP were significantly elevated in CAD patients with double/triple-vessel disease. Our results demonstrated alterations in A-FABP levels with severity of CAD and, therefore, indirectly support the hypothesis of an active role for A-FABP in the pathogenesis of CAD.

Bariatric surgery in morbidly obese patients improves the atherogenic qualitative properties of the plasma lipoproteins.

OBJECTIVE: The purpose of this study was to evaluate the effect of weight loss induced in morbidly obese subjects by Roux-en-Y gastric bypass bariatric surgery on the atherogenic features of their plasma lipoproteins. METHODS: Twenty-one morbidly obese subjects undergoing bariatric surgery were followed up for up to 1 year after surgery. Plasma and lipoproteins were assayed for chemical composition and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity. Lipoprotein size was assessed by non-denaturing polyacrylamide gradient gel electrophoresis, and oxidised LDL by ELISA. Liver samples were assayed for mRNA abundance of oxidative markers. RESULTS: Lipid profile analysis revealed a reduction in the plasma concentrations of cholesterol and triglycerides, which were mainly associated with a significant reduction in the plasma concentration of circulating apoB-containing lipoproteins rather than with changes in their relative chemical composition. All patients displayed a pattern A phenotype of LDL subfractions and a relative increase in the antiatherogenic plasma HDL-2 subfraction (>2-fold; P < 0.001). The switch towards predominantly larger HDL particles was due to an increase in their relative cholesteryl ester content. Excess weight loss also led to a significant decrease in the plasma concentration of oxidised LDL (∼-25%; P < 0.01) and in the total Lp-PLA2 activity. Interestingly, the decrease in plasma Lp-PLA2 was mainly attributed to a decrease in the apoB-containing lipoprotein-bound Lp-PLA2. CONCLUSION: Our data indicate that the weight loss induced by bariatric surgery ameliorates the atherogenicity of plasma lipoproteins by reducing the apoB-containing Lp-PLA2 activity and oxidised LDL, as well as increasing the HDL-2 subfraction.

Lipoprotein-associated phospholipase A2 and carotid intima-media thickness in individuals classified as low-risk according to Framingham.

BACKGROUND: The Framingham risk score (FRS) has long been used as a global tool to estimate coronary heart disease (CHD) risk, but data has shown that subclinical CHD may exist in those classified as low risk by FRS, and as a result, there is potential for misclassification. Lipoprotein-associated phospholipase A2 (Lp-PLA2) and carotid intima-media thickness (CIMT) are two emerging risk markers that are predictive of future CHD events. PURPOSE: To examine Lp-PLA2 and CIMT values in low risk individuals, and to explore the relationship between Lp-PLA2 and CIMT. METHODS: A total of 229 men and women (age =53±7 years) underwent body composition analysis, objective physical activity measurement, fasting blood draw to determine standard lipid values and Lp-PLA2 mass, and CIMT measurement through ultrasound. RESULTS: For all subjects, mean CIMT was 0.61±0.1 mm, mean Lp-PLA2 mass was 197±45 ng/dL. A total of 19.5% and 34.6% of women and 4.6% and 73.8% of men were considered at elevated risk for CHD by CIMT (>75(th) percentile for age) and Lp-PLA2 mass (>200 ng/dL) standards, respectively. Both CIMT and Lp-PLA2 mass were significant independent predictors of each other, whereas traditional risk markers (lipids, glucose) were not. CONCLUSIONS: Results suggest that in those classified as low risk by FRS, evidence of increased CHD risk may exist through the use of newer risk markers like CIMT and Lp-PLA2. These emerging markers may aid in the earlier detection and intervention of subclinical CHD.

Everolimus therapy is associated with reduced lipoprotein-associated phospholipase A2 (Lp-Pla2) activity and oxidative stress in heart transplant recipients.

BACKGROUND: Several studies demonstrated decreased severity and incidence of cardiac allograft vasculopathy (CAV) in heart transplant recipients receiving immunosuppressive therapy with everolimus. However, data regarding the influence of everolimus on risk factors predisposing to CAV are hitherto limited. We here systematically evaluated cardiovascular risk factors in heart transplanted patients, who underwent conversion to everolimus or were maintained on conventional therapy with calcineurin inhibitors (CNI). METHODS: 50 Patients receiving everolimus and 91 patients receiving CNI in addition to mycophenolate mofetil and low-dosed steroids were included in the study. CAV risk factors were determined in plasma or urine using standard enzymatic or immunochemical methods. RESULTS: No significant differences were observed between both groups with regard to lipid (total, LDL- and HDL-cholesterol), metabolic (glucose, insulin), inflammatory (C-reactive protein, IL-6, myeloperoxidase) and cardiac (troponin I, NT-proBNP) risk factors. However, significantly lower activity of lipoprotein-associated phospholipase A2 (Lp-PLA2) and a negative correlation between the Lp-PLA2 activity and the everolimus concentration were observed in plasmas from everolimus-treated patients. Conversion to everolimus significantly lowered Lp-PLA2 activity in heart transplant recipients. Studies in vitro revealed reduced Lp-PLA2 expression in hepatocytes and macrophages pre-exposed to everolimus. In addition, reduced plasma markers of oxidative stress including oxidized LDL, 8-iso-prostaglandin F2α and protein carbonyls were noted in heart transplant recipients receiving everolimus therapy. CONCLUSION: Our results suggest that everolimus specifically lowers plasma activity and cellular production of Lp-PLA2 and thereby dampens oxidative stress. These effects may additionally contribute to the reduced CAV incidence observed in heart transplant recipients receiving everolimus therapy.

Correlation of Traditional Chinese Medicine Syndrome Types of Hypertension with Carotid Artery Intima-media Thickness and Plasma Lp-PLA2 Expression / 广州中医药大学学报

Objective To explore the correlation of traditional Chinese medicine (TCM) syndrome types of hypertension with carotid artery intima-media thickness (IMT) and plasma lipoprotein-associated phospholipase A2 (Lp-PLA2),so as to provide a TCM therapy for early prevention and treatment of hypertension and its complications in clinic.Methods We collected a total of 170 cases of hypertension patients,55 with kidney-essence insufficiency syndrome,50 with ascendant hyperactivity of liver yang syndrome,and 65 with phlegm-damp retention in middle energizer syndrome.IMT was measured by the carotid Doppler ultrasound,and plasma Lp-PLA2 expression was examined by enzyme-linked immunosorbent assay.And then the differences of IMT and Lp-PLA2 expression among the three groups were compared and analyzed.Results There were significant differences of carotid artery IMT and Lp-PLA2 among the three groups(P＜ 0.01),and the number of patients with carotid atherosclerosis and the expression level of Lp-PLA2 in the group of phlegm-damp retention in middle energizer syndrome were higher than those intheothertwogroups(P＜0.01).Conclusion Differentiation treatment based on phlegm may be more conducive to the prevention and treatment of hypertension and its complications.

Biomarkers and their involvement in the early diagnosis of right ventricular dysfunction in type 2 Diabetes Mellitus.

OBJECTIVE: During the last years, left ventricular dysfunction in diabetes was intensely studied and it is recognized as a complication of diabetes, while data regarding the right ventricular dysfunction is still incomplete. The aim of this study was to find a correlation between inflammatory biomarkers, adiponectin and right ventricular strain and strain rate properties in patients with diabetes mellitus type 2. METHODS: We studied 29 patients with type 2 diabetes mellitus (DM), with coexisting cardiovascular complications, coronary artery disease and high blood pressure (group 1- DM+CV, aged 61.2 ± 4.2 years); and 22 patients with type 2 diabetes and controlled high blood pressure only, with no other coexisting cardiovascular complications (group 2- DM, aged 60.86 ± 4.4 years). We evaluated the right ventricular (rv) function through vector velocity imaging (vvi)and determined the inflammatory profile through assessment of the following biomarkers: high sensitivity C- reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-alfa), lipoprotein associated phospholipase A2 (Lp-PLA2) and adiponectin level for each patient. RESULTS: VVI revealed significantly lower values of systolic strain and strain rates (SR) in the basal segment of the RV free wall in group I patients (DM+CV) as compared to group II patients (DM) which indicates higher impairment of RV systolic function in patients with diabetes and other cardiovascular complications. In both groups strain and strain rate values were correlated with Lp-PLA2 activity levels. CONCLUSIONS: In Type 2 diabetes mellitus we identified a low-grade inflammatory status correlated with right ventricular systolic dysfunction.