Adiponectin, ghrelin, and leptin differentially influence human platelet and human vascular endothelial cell functions: Implication in obesity-associated cardiovascular diseases

Elbatarny, Hisham S.; Netherton, Stuart J.; Ovens, Jeffrey D.; Ferguson, Alastair V.; Maurice, Donald H.

doi:10.1016/j.ejphar.2006.11.052

Cited by 60 publications

(45 citation statements)

References 29 publications

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“…This C.I. interacts with 6:133.92-142.67 Mb, which harbors Pde3a, a locus known to be downstream of ghrelin signaling in platelets (Elbatarny et al 2007) and which shows significant differences in gene expression in white fat between SM/J and LG/J (P ¼ 0.00018) and 12:73.42-89.12 Mb, which contains Hif1a, whose protein product increases the expression of Vegf (Hoffmann et al 2008). Interestingly, Vegfc shows a significant difference in expression in white fat between the parental lines (P ¼ 0.001) and Vegfb shows differences in liver (P ¼ 0.009).…”

Section: Resultsmentioning

confidence: 99%

Mapping the Epistatic Network Underlying Murine Reproductive Fatpad Variation

Jarvis

Cheverud

2011

Genetics

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Genome-wide mapping analyses are now commonplace in many species and several networks of interacting loci have been reported. However, relatively few details regarding epistatic interactions and their contribution to complex trait variation in multicellular organisms are available and the identification of positional candidate loci for epistatic QTL (epiQTL) is hampered, especially in mammals, by the limited genetic resolution inherent in most study designs. Here we further investigate the genetic architecture of reproductive fatpad weight in mice using the F 10 generation of the LG,SM advanced intercross (AI) line. We apply multiple mapping techniques including a single-locus model, locus-specific composite interval mapping (CIM), and tests for multiple QTL per chromosome to the 12 chromosomes known to harbor single-locus QTL (slQTL) affecting obesity in this cross. We also perform a genome-wide scan for pairwise epistasis. Using this combination of approaches we detect 199 peaks spread over all 19 autosomes, which potentially contribute to trait variation including all eight original F 2 loci (Adip1-8), novel slQTL peaks on chromosomes 7 and 9, and several novel epistatic loci. Extensive epistasis is confirmed involving both slQTL confidence intervals (C.I.) as well as regions that show no significant additive or dominance effects. These results provide important new insights into mapping complex genetic architectures and the role of epistasis in complex trait variation.

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Section: Resultsmentioning

confidence: 99%

Mapping the Epistatic Network Underlying Murine Reproductive Fatpad Variation

Jarvis

Cheverud

2011

Genetics

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“…The full-length form of adiponectin and the recombinant globular domain both protected the integrity of the endothelial barrier. While this work was being prepared for submission, Elbatarny et al 17 reported that adiponectin increased the integrity of a microvascular endothelial cell monolayer to the passage of fluorescein-conjugated dextran; however, the signaling mechanism of adiponectin was not evaluated.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin Protects Against Angiotensin II or Tumor Necrosis Factor α–Induced Endothelial Cell Monolayer Hyperpermeability

Mahadev

et al. 2008

ATVB

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Objective-Angiotensin II (Ang II) and tumor necrosis factor (TNF)-␣ levels increase endothelial permeability, and we hypothesized that adiponectin suppressed these responses in a cAMP-dependent manner. Methods and Results-The effect of adiponectin on transendothelial electric resistance (TEER) and diffusion of albumin through human umbilical vein and bovine aortic endothelial cell monolayers induced by Ang II (100 nmol/L) or TNF-␣ (5 ng/mL) was measured.

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“…The kind of recombinant adiponectin employed is of relevance, as this study showed that recombinant globular adiponectin, but not full-length adiponectin, stimulated platelet aggregation and dense granule secretion. Another study found that low concentrations of adiponectin (Ͻ0.5 g/ml) did not influence the effects of ADP and collagen on platelet adhesion (5).…”

Section: Discusionmentioning

confidence: 99%

Adiponectin diminishes platelet aggregation and sCD40L release. Potential role in the metabolic syndrome

Restituto¹,

Colina²,

Varo

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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(CD40L), is increased in the metabolic syndrome (MS) and released from platelets. We hypothesized that adiponectin modulates platelet function, and we sought to evaluate the association of adiponectin and sCD40L levels with platelet aggregation in MS and the effects of adiponectin on platelet aggregation and activation. Platelet aggregation and circulating adiponectin, sCD40L and P-selectin were determined in 30 controls and 30 patients with MS. Also, in vitro studies were performed in platelet-rich plasma from nine healthy volunteers. Adiponectin receptors were demonstrated by Western blotting and flow cytometry. ADP and epinephrine platelet aggregation was measured after preincubation with adiponectin. sCD40L and P-selectin secretion was measured in the supernatants by ELISA. Patients with MS had higher sCD40L and P-selectin than controls (5.96 Ϯ 0.50 vs. 4.28 Ϯ 0.41 ng/ml, P Ͻ 0.05, and 151 Ϯ 8 vs. 122 Ϯ 9 ng/ml, P Ͻ 0.05). By contrast, adiponectin was lower in patients with MS than in controls (5.25 Ϯ 0.30 vs. 7.35 Ϯ 0.34 g/ml, P Ͻ 0.001). Higher platelet aggregation was found in MS. Adiponectin inversely correlated with P-selectin (R ϭ Ϫ0.35, P ϭ 0.009), sCD40L (r ϭ Ϫ0.24, P ϭ 0.05) and epinephrine and collagen induced aggregation (r ϭ Ϫ0.80, P ϭ 0.005; r ϭ Ϫ0.70, P ϭ 0.011). Platelets express the receptors for adiponectin. Platelet aggregatory response to epinephrine and ADP significantly decreased following preincubation with adiponectin (96 Ϯ 4 vs. 23 Ϯ 3%, P Ͻ 0.001, and 102 Ϯ 9 vs. 85 Ϯ 9%, P ϭ 0.004). Adiponectin prevented platelet sCD40L release (1.63 Ϯ 0.15 vs. 2.04 Ϯ 0.20 ng/ml, P Ͻ 0.001). Enhanced platelet aggregation and activation markers are found in MS associated with low adiponectin concentrations. Novel evidence is provided demonstrating that adiponectin has antithrombotic properties, since it inhibits platelet aggregation and platelet activation. soluble CD40 ligand; platelets; platelet activation; P-selectin THE METABOLIC MYNDROME (MS) consists of the convergence of a variety of risk factors in the same individual and is characterized by a general proinflammatory and prothrombotic state that interacts synergistically, causing or accelerating the progression of atherosclerosis. There are different definitions to describe this syndrome. Currently, the more accepted definitions are those of the National Cholesterol Education Program -Third Adult Treatment Panel (NCEP ATP III) and the World Health Organization (WHO). In both, obesity, insulin resistance, dyslipidemia, and hypertension are considered to underlie the metabolic syndrome. Prothrombosis is not yet included in any definition of MS, but the International Diabetes Federation (IDF) consensus group identifies a prothrombotic state related to MS and advises investigating the predictive power of these extra criteria for cardiovascular risk or diabetes. In fact, several investigations demonstrate the association between a prothrombotic state and diabetes (23), obesity (20), and hypertension (17).Furthermore, recent studies demonstrate th...

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Adiponectin, ghrelin, and leptin differentially influence human platelet and human vascular endothelial cell functions: Implication in obesity-associated cardiovascular diseases

Cited by 60 publications

References 29 publications

Mapping the Epistatic Network Underlying Murine Reproductive Fatpad Variation

Mapping the Epistatic Network Underlying Murine Reproductive Fatpad Variation

Adiponectin Protects Against Angiotensin II or Tumor Necrosis Factor α–Induced Endothelial Cell Monolayer Hyperpermeability

Adiponectin diminishes platelet aggregation and sCD40L release. Potential role in the metabolic syndrome

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