Interactions Between Lipoproteins and Platelet Membranes in Obesity
ABSTRACT The aim was to investigate low-density lipoprotein (LDL) composition and Na(+)/K(+) adenosine triphosphatase (ATPase) and Ca(2+) ATPase activities and membrane fluidity measured by 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) in platelets from obese patients and controls in order to identify, if any, platelet membrane's chemical-physical and/or functional modifications associated with compositional modification of circulating lipoproteins. Moreover, we studied the in vitro effect on both platelet transmembrane cationic transport and fluidity, by incubating LDL from 30 obese subjects with platelets from 30 control subjects. The analysis of the chemical composition of LDL from obese patients showed a significant increase in the percent content of total cholesterol (TC) and triglycerides (TGs) and in the mean levels of lipid hydroperoxides compared to controls' LDL. Platelet Na(+)/K(+) ATPase and Ca(2+) ATPase activities showed, respectively, a significant decrease and increase in patients compared to controls; minor significant, respectively, decreases and increases are shown also in control platelets incubated with LDL from obese patients. Anisotropy tested with TMA-DPH probe was significantly increased both in platelets from obese patients and in control platelets incubated with LDL from obese patients compared to control platelets. This study highlights that obesity induces remarkable modifications both in lipoproteins and platelets. Both platelet hyperfunction and quantitative/qualitative alterations in plasma lipoproteins, as well as an altered interaction between circulating lipoproteins and platelets, might play a relevant role in the increased prevalence of the early atherosclerotic lesions development in obese subjects. The present data point out that obesity might represent a major potentially modifiable risk factor for the onset of numerous complications, in particular cardiovascular ones.
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ABSTRACT: Obesity is associated with increased cardiovascular disease. Metabolic syndrome (MS) identifies substantial additional cardiovascular risk beyond the individual risk factors, and is a powerful predictor of cardiovascular events even regardless of body mass index, thus suggesting a common downstream pathway conferring increased cardiovascular risk. Platelet hyper-reactivity/activation plays a central role to accelerate atherothrombosis and is the result of the interaction among the features clustering in obesity and MS: insulin resistance, inflammation, oxidative stress, endothelial dysfunction. Interestingly, the same pathogenic events largely account for the less-than-expected response to antiplatelet agents, namely low-dose aspirin. The proposed explanations for this phenomenon, besides underdosing of drug and/or reduced bioavailability, subsequent to excess of adipose tissue, include enhanced platelet turnover, leading to unacetylated COX-1 and COX-2 in newly formed platelets as a source of aspirin-escaping thromboxane formation; extraplatelet sources of thromboxane, driven by inflammatory triggers; and enhanced lipid peroxidation, activating platelets with a mechanism bypassing COX-1 acetylation or limiting COX-isozyme acetylation by aspirin. This review will address the complex interactions between platelets and the pathogenic events occurring in obesity and MS, trying to translate this body of mechanistic information into a clinically relevant read-out, in order to establish novel strategies in the prevention/treatment of atherothrombosis.Obesity Reviews 09/2011; 13(1):27-42. DOI:10.1111/j.1467-789X.2011.00930.x · 7.86 Impact Factor
Article: Adipokines and thrombosis[Show abstract] [Hide abstract]
ABSTRACT: 1. Obesity is a major risk factor for cardiovascular disease. An increased body mass index (BMI) is associated with venous thromboembolism, myocardial infarction, stroke and stent thrombosis after percutaneous interventions. Studies in mouse models of obesity and induced arterial or venous thrombosis have provided insights into the mechanisms involved. 2. In addition to elevated circulating levels of fibrinogen, factor VII and plasminogen activator inhibitor (PAI)-1, changes in platelet biology and function may underlie the increased (athero) thrombotic risk in obesity. These include elevated platelet counts, an increase in mean platelet volume, an increased platelet aggregatory response to agonists and a reversible resistance to the anti-aggregatory effects of nitric oxide and prostacyclin I(2) . 3. Specific adipokines mediate the prothrombotic state in obesity. Of these, leptin enhances both arterial and venous thrombosis by promoting platelet adhesion, activation and aggregation. Leptin also induces tissue factor expression by human neutrophils and other cells. C-Reactive protein enhances the formation of monocyte-platelet aggregates and also promotes P-selectin expression and platelet adhesion to endothelial cells. Further, the adipose tissue is a significant source of tissue factor and PAI-1. Conversely, the circulating levels of adiponectin, a hormone that exerts vasculoprotective, anti-atherosclerotic and antithrombotic effects, are reduced in obese individuals. 4. A better understanding of the interactions of the adipose tissue with circulating and vascular cells and the dissection of the mechanisms linking adipokines to arterial and venous thrombosis may identify obese individuals at particularly high cardiovascular risk and indicate promising vasculoprotective and therapeutic targets.Clinical and Experimental Pharmacology and Physiology 08/2011; 38(12):864-71. DOI:10.1111/j.1440-1681.2011.05589.x · 2.41 Impact Factor
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ABSTRACT: Evidence suggests that serum brain-derived neurotrophic factor (serum BDNF) can be affected by cardiorespiratory fitness (CRF), but this relationship is far from clear. Recent reports show an inverse relationship between serum BDNF and CRF in healthy individuals, and other studies suggest a possible association between serum BDNF and cardiovascular disease. However, the possible interaction between serum BDNF, CRF, and cardiovascular disease risk has not been studied. The purpose of this study was to examine the association among serum BDNF, CRF, and cardiovascular disease risk factors in healthy men. The investigation involved a large sample of men (n = 995, age range: 20-76 years) who live in the central area of South Korea and were recruited into the Preventive Health Study. Our study showed a significant inverse relationship between serum BDNF and relative VO(2)max (r = -0.412, p < 0.0001) and heart rate reserve (r = -0.194, p < 0.0001). Serum BDNF was positively correlated with body mass index (r = 0.80, p < 0.0001), total cholesterol (r = 0.185, p < 0.0001), and triglyceride (r = 0.320, p < 0.0001). Our data suggest that serum BDNF may be associated with effects of increased CRF on cardiovascular disease. However, more research is clearly needed before a determination of whether, and to what extent, serum BDNF may be responsible for some of the health benefits associated with CRF.Arbeitsphysiologie 09/2010; 111(2):303-11. DOI:10.1007/s00421-010-1658-5 · 2.30 Impact Factor