Iván Palomo

Antiphospholipid Antibodies and the Antiphospholipid Syndrome: Pathogenic Mechanisms

Antiphospholipid antibodies (Abs) are associated with thrombosis and are a risk factor for recurrent pregnancy loss and obstetric complications in patients with the antiphospholipid syndrome. It is generally accepted that the major autoantigen for aPL Abs is beta (2) glycoprotein I, which mediates the binding of aPL Abs to target cells (i.e., endothelial cells, monocytes, platelets, trophoblasts, etc.) leading to thrombosis and fetal loss. This article addresses molecular events triggered by aPL Abs on endothelial cells, platelets, and monocytes and complement activation, as well as a review of the current knowledge with regard to the putative receptor(s) recognized by aPL Abs on target cells as well as novel mechanisms that involve fibrinolytic processes. A section is devoted to the description of thrombotic and inflammatory processes that lead to obstetric complications mediated by aPL Abs. Based on experimental evidence using in vitro and in vivo models, new targeted therapies for treatment and/or prevention of thrombosis and pregnancy loss in antiphospholipid syndrome are proposed.

Mechanisms of Chronic State of Inflammation as Mediators That Link Obese Adipose Tissue and Metabolic Syndrome

The metabolic syndrome is a cluster of cardiometabolic alterations that include the presence of arterial hypertension, insulin resistance, dyslipidemia, and abdominal obesity. Obesity is associated with a chronic inflammatory response, characterized by abnormal adipokine production, and the activation of proinflammatory signalling pathways resulting in the induction of several biological markers of inflammation. Macrophage and lymphocyte infiltration in adipose tissue may contribute to the pathogenesis of obesity-mediated metabolic disorders. Adiponectin can either act directly on macrophages to shift polarization and/or prime human monocytes into alternative M2-macrophages with anti-inflammatory properties. Meanwhile, the chronic inflammation in adipose tissue is regulated by a series of transcription factors, mainly PPARs and C/EBPs, that in conjunction regulate the expression of hundreds of proteins that participate in the metabolism and storage of lipids and, as such, the secretion by adipocytes. Therefore, the management of the metabolic syndrome requires the development of new therapeutic strategies aimed to alter the main genetic pathways involved in the regulation of adipose tissue metabolism.

Elevated concentration of asymmetric dimethylarginine (ADMA) in individuals with metabolic syndrome

The metabolic syndrome (MS) is a cluster of pathophysiological alterations that includes the presence of hypertension, insulin resistance, dyslipidemia, and abdominal obesity. MS is associated with increased risk of developing diabetes and cardiovascular diseases. Endothelial dysfunction with impaired nitric oxide (NO) bioavailability has been implicated in insulin resistance and hypertension. NO is synthesized by nitric oxide synthase (NOS) using l-arginine as substrate. Asymmetric dimethyl arginine (ADMA) is a major and potent endogenous NOS inhibitor, associated with cardiovascular and renal diseases. We tested the hypothesis that plasmatic ADMA levels are increased in patients with MS. We studied 85 adult individuals from Talca, Chile, separated in two groups, 48 individuals with MS (according to modified ATP III criteria), and 37 individuals without MS as controls. ADMA levels were significantly increased in the MS group (mean±standard deviation 0.71±0.38 vs. 0.48±0.28μmol/L, p=0.0009). Furthermore, the levels of ADMA were modestly but significantly correlated with waist circumference (p=0.01) but not with the other components of MS (blood pressure, glycemia, triglycerides and high density lipoprotein cholesterol HDL-c). These results suggest a possible link between increased ADMA levels and the MS.

Evaluation of metabolic syndrome in adults of Talca city, Chile

Objective-Insulin resistance (IR) is an important risk factor for type 2 Diabetes Mellitus (DM2) and cardiovascular disease (CVD). Metabolic Syndrome (MS) is a clustering of metabolic alterations associated to IR; however, there is no international consensus for defining its diagnosis. Our objective was to evaluate the prevalence and characteristics of MS identified by the ATP III and IDF criteria in adults from Talca city.Research and methods-We studied 1007 individuals, aged 18–74, and residents from Talca. MS subjects were defined according to ATP III (three altered factors) and IDF criteria (patients with waist circumference >80/90 cm (W/M) and two others altered factors).Results-The prevalence of metabolic syndrome according to the IDF and ATP III criteria was 36.4% and 29.5%, respectively after adjustment for age and sex. The agreement for both criteria was 89%. The prevalence in men was higher than in women for both MS definitions, although not significant. MS probability increased with age, and the highest risk was in the 57–68 age group (ATP-MS) and 53–72 age group (IDF-MS). Hypertension, high triglycerides and abdominal obesity are the most frequent alterations in MS.Conclusion-MS prevalence in adults was higher when diagnosed with IDF than with ATP criterion; in both, age is directly related with the MS presence. The MS subjects showed higher levels of blood pressure, waist circumference and plasma triglycerides. Considering our results, it is worrisome that one third of our population has a high risk of developing DM2 and CVD in the future.

Role of PPARs in inflammatory processes associated with metabolic syndrome (Review).

Metabolic syndrome (MS) includes the presence of arterial hypertension, insulin resistance, dyslipidemia, cardiovascular disease (CVD) and abdominal obesity, which is associated with a chronic inflammatory response, characterized by abnormal adipokine production, and the activation of certain pro-inflammatory signaling pathways. Furthermore, the changes presented by the adipose tissue in MS favors the secretion of several molecular mediators capable of activating or suppressing a number of transcription factors, such as the peroxisome proliferator-activated receptors (PPARs), whose main functions include storage regulation and fatty acid catabolization. When they are activated by their ligands (synthetic or endogenous), they control several genes involved in intermediate metabolism, which make them, together with the PPAR gamma coactivator-1-α (PGC-1) and the silent information regulator T1 (SIRT1), good targets for treating metabolic diseases and their cardiovascular complications.

Intervention with education and exercise reverses the metabolic syndrome in adults

About 29% of the adult population of Talca, Chile, suffers from the metabolic syndrome (MS), a value higher than the national prevalence. Evidence indicates that exercise and nutritional changes reduce the predominance of this syndrome. The goal of this study was to evaluate the effects of a structured interventional program of physical activity and nutritional counseling in adults with MS. Fifty-one subjects were studied: 27 were included in the interventional program (I-MS). The control group was formed by 24 individuals who did not participate in the program (NI-MS). We assessed body weight, corporal composition, arterial pressure, glycemia, and lipid profile at baseline and after 18 weeks of treatment. After this period, the I-SM group showed a significant decrease in triglycerides (geometric mean 202.2 to 110.5 mg/dL, P < .001), diastolic blood pressure (mean 85.4 to 79.6 mm Hg, P = .001), waist circumference (mean men 101.5 to 94.1 cm, P < .001; mean women 107.2 to 96.2 cm, P < .001), weight (mean 81.1 to 77.2 kg, P < .001), and body mass index (mean 31.8 to 30.2 kg/m(2), P < .001). In the NI-MS group, the individual parameters did not change significantly. Our results show that a non-pharmacological treatment based on exercise exerts an important beneficial effect in patients with MS, mainly on the waist circumference, blood pressure, and triglycerides.

Antiplatelet, anticoagulant, and fibrinolytic activity in vitro of extracts from selected fruits and vegetables

A diet rich in fruits and vegetables is known to decrease the risk of cardiovascular disease. However, the information regarding the antithrombotic activity (antiplatelet, anticoagulant, and fibrinolytic) of fruits and vegetables is scarce. The aim of this study was to assess the antithrombotic activity of extracts from fruits and vegetables widely consumed in central Chile. The study included samples of 19 fruits and 26 vegetables, representative of the local diet. The extracts prepared from each sample included an aqueous (juice or pressed solubles) and/or methanol-soluble fraction. The extracts were evaluated for antiplatelet, anticoagulant, and fibrinolytic activity in vitro at a final concentration of 1 mg/ml. The antiplatelet activity was assessed by platelet aggregation inhibition; anticoagulant activity was measured by the prothrombin time (PT), diluted prothrombin time (dPT), activated partial thromboplastin time (APTT), kaolin clotting time (KCT), and thrombin time. The fibrinolytic effect was determined with the euglobin clot lysis time and fibrin plate methods. Extracts of green beans and tomatoes inhibited platelet aggregation induced by ADP and arachidonic acid, in a concentration-dependent manner. The methanolic extracts of grapes prolonged the PT and dPT. Finally, extracts of raspberry prolonged the APTT and also presented fibrinolytic activity. In conclusion, from a screening that included a variety of fruits and vegetables, we found antiplatelet activity in green beans and tomatoes, anticoagulant activities in grapes and raspberries, whereas fibrinolytic activity was observed only in raspberries. Further investigations are necessary to advance in knowledge of the active compounds of these fruits and vegetables and their mechanisms of action.

Estimación de riesgo de enfermedad coronaria mediante la función de Framingham adaptada para la población chilena

The Framingham function was adapted for a populationaged 35 to 74 years, based on an estimate of Chilean incidence of coronary heart disease and theprevalence of coronary heart disease risk factors such as age, sex, total cholesterol, high-densitylipoprotein cholesterol, blood pressure, diabetes and smoking.

Chlorogenic Acid Inhibits Human Platelet Activation and Thrombus Formation

Background Chlorogenic acid is a potent phenolic antioxidant. However, its effect on platelet aggregation, a critical factor in arterial thrombosis, remains unclear. Consequently, chlorogenic acid-action mechanisms in preventing platelet activation and thrombus formation were examined. Methods and Results Chlorogenic acid in a dose-dependent manner (0.1 to 1 mmol/L) inhibited platelet secretion and aggregation induced by ADP, collagen, arachidonic acid and TRAP-6, and diminished platelet firm adhesion/aggregation and platelet-leukocyte interactions under flow conditions. At these concentrations chlorogenic acid significantly decreased platelet inflammatory mediators (sP-selectin, sCD40L, CCL5 and IL-1β) and increased intraplatelet cAMP levels/PKA activation. Interestingly, SQ22536 (an adenylate cyclase inhibitor) and ZM241385 (a potent A2A receptor antagonist) attenuated the antiplatelet effect of chlorogenic acid. Chlorogenic acid is compatible to the active site of the adenosine A2A receptor as revealed through molecular modeling. In addition, chlorogenic acid had a significantly lower effect on mouse bleeding time when compared to the same dose of aspirin. Conclusions Antiplatelet and antithrombotic effects of chlorogenic acid are associated with the A2A receptor/adenylate cyclase/cAMP/PKA signaling pathway.

Strawberry extract presents antiplatelet activity by inhibition of inflammatory mediator of atherosclerosis (sP-selectin, sCD40L, RANTES, and IL-1β) and thrombus formation

Abstract Cardiovascular disease prevention is of high priority in developed countries. Healthy eating habits including the regular intake of an antithrombotic diet (fruit and vegetables) may contribute to prevention. Platelet function is a critical factor in arterial thrombosis and the effect strawberries have is still unclear. Therefore, the aim of this study was to systematically examine the action of strawberries in preventing platelet activation and thrombus formation. Strawberry extract concentration-dependently (0.1–1 mg/ml) inhibited platelet aggregation induced by ADP and arachidonic acid. At the same concentrations as strawberry inhibits platelet aggregation, it significantly decreased sP-selectin, sCD40L, RANTES, and IL-1β levels. The strawberry may exert significant protective effects on thromboembolic-related disorders by inhibiting platelet aggregation. Also, this suggests that antithrombotic activity may have novel anti-inflammatory effects.