Alterations in cell adhesion molecules and other biomarkers of cardiovascular disease in patients with metabolic syndrome

Rosso, Leonardo Gómez; Benitez, María Belén; Fornari, María Cecilia; Berardi, Vanina E.; Lynch, Santiago; Schreier, Laura; Wikinski, Regina; Cuniberti, Luis; Brites, Fernando

doi:10.1016/j.atherosclerosis.2007.11.007

Cited by 42 publications

(34 citation statements)

References 55 publications

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“…21 Ridker and colleagues 22 and Rutter and colleagues 23 showed a significant association between serum concentrations of hs-CRP and various components of MS. Festa and colleagues 24 showed in the Insulin Resistance and Atherosclerosis Study study a positive correlation of hs-CRP with IR and other components of MS. Alterations in VCAM-1 in subjects with MS have been shown in other populations. 20,25 Our study results show agreement with these findings. In contrast, Vaverkova and colleagues 26 demonstrated VCAM-1 to have a positive association with adiponectin, a potential antiinflammatory adipocytokine in patients with cardiovascular disease (CVD) and dyslipidemia.…”

Section: Discussionsupporting

confidence: 95%

High Sensitivity C-Reactive Protein, Tumor Necrosis Factor-α, Interleukin-6, and Vascular Cell Adhesion Molecule-1 Levels in Asian Indians with Metabolic Syndrome and Insulin Resistance (CURES-105)

Indulekha

Surendar

Mohan³

2011

J Diabetes Sci Technol

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Section: Discussionsupporting

confidence: 95%

High Sensitivity C-Reactive Protein, Tumor Necrosis Factor-α, Interleukin-6, and Vascular Cell Adhesion Molecule-1 Levels in Asian Indians with Metabolic Syndrome and Insulin Resistance (CURES-105)

Indulekha

Surendar

Mohan³

2011

J Diabetes Sci Technol

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“…Low-grade inflammation has been closely associated with both insulin resistance and the progression of type 2 diabetes as indicated by increased levels of cell adhesion molecules (e.g., VCAM-1, ICAM-1, and E-selectin), interleukins (e.g., TNF-␣), oxidative stress, and activation and translocation of NF-B (74,191,203). Downregulation of the inhibitor of NF-B kinase-␤, a serine/threonine kinase involved in the phosphorylation of IB, prevented the TNF-␣-induced insulin resistance in skeletal muscle (7).…”

Section: Protein O-glcnacylation and Cardiovascular Protectionmentioning

confidence: 99%

ProteinO-GlcNAcylation: a new signaling paradigm for the cardiovascular system

Laczy¹,

Hill²,

Wang³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

141

135

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The posttranslational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide ␤-N-acetylglucosamine (O-GlcNAc) is a highly dynamic and ubiquitous protein modification. Protein O-GlcNAcylation is rapidly emerging as a key regulator of critical biological processes including nuclear transport, translation and transcription, signal transduction, cytoskeletal reorganization, proteasomal degradation, and apoptosis. Increased levels of O-GlcNAc have been implicated as a pathogenic contributor to glucose toxicity and insulin resistance, which are both major hallmarks of diabetes mellitus and diabetes-related cardiovascular complications. Conversely, there is a growing body of data demonstrating that the acute activation of O-GlcNAc levels is an endogenous stress response designed to enhance cell survival. Reports on the effect of altered O-GlcNAc levels on the heart and cardiovascular system have been growing rapidly over the past few years and have implicated a role for O-GlcNAc in contributing to the adverse effects of diabetes on cardiovascular function as well as mediating the response to ischemic injury. Here, we summarize our present understanding of protein O-GlcNAcylation and its effect on the regulation of cardiovascular function. We examine the pathways regulating protein O-GlcNAcylation and discuss, in more detail, our understanding of the role of O-GlcNAc in both mediating the adverse effects of diabetes as well as its role in mediating cellular protective mechanisms in the cardiovascular system. In addition, we also explore the parallels between O-GlcNAc signaling and redox signaling, as an alternative paradigm for understanding the role of O-GlcNAcylation in regulating cell function. hexosamine biosynthesis; protein O-glycosylation; ␤-N-acetylglucosamine transferase; diabetes mellitus POSTTRANSLATIONAL MODIFICATION (PTM) of proteins is a common mechanism for the modulation of protein function, location, and turnover. Although protein phosphorylation is probably the most widely studied form of PTM, there are many other PTMs, including acylation, ubiquitylation, methylation, acetylation, thiolation, nitration, and glycosylation (107). The focus of this review is protein glycosylation, specifically, O-glycosylation of nuclear and cytoplasmic proteins. Classical protein glycosylation occurs in the endoplasmic reticulum and Golgi, leading to the formation of stable and complex elongated oligosaccharide structures via both N-linkage on asparagine and O-linkage on the hydroxy amino acids serine and threonine in addition to hydroxyproline, hydroxylysine, and tyrosine residues of proteins that become secreted or membrane component glycoproteins (189). In contrast, glycosylation of nuclear and cytoplasmic proteins is a rapid and dynamic modification of serine or threonine residues by the O-linked attachment of the monosaccharide ␤-N-acetylglucosamine (OGlcNAc) (97,195); this process is referred to as protein O-GlcNAcylation to contrast it wi...

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“…For example, serum levels of sVCAM-1 were found to be higher in MS patients (17±5 ng/ ml) than in a control group (13±4 ng/ml) (22). These patients had high plasmatic levels of inflammatory biomarkers (23).…”

Section: Discussionmentioning

confidence: 95%

Increased concentrations of soluble vascular cell adhesion molecule-1 and soluble CD40L in subjects with metabolic syndrome

Palomo

Jaramillo²,

Alarcón³

et al. 2009

Mol Med Rep

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Abstract. Metabolic syndrome (MS) is associated with a high incidence rate of cardiovascular disease. It is characterized by abdominal obesity, elevated blood pressure, atherogenic dyslipidemia [high LDL-c (low density lipoprotein cholesterol) and low HDL-c (high density lipoprotein cholesterol)] and insulin resistance or glucose intolerance. In the context of MS, alterations in the plasmatic levels of some soluble forms of cell adhesion molecules can appear, e.g., soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin) and soluble CD40L (sCD40L). The objective of this study was to compare the serum levels of sVCAM-1, sE-selectin and sCD40L in MS and non-MS groups and to associate these molecules with the diagnostic criteria of MS. A total of 185 non-smokers between 45 and 64 years of age were included. Of these, 93 corresponded to the MS group and the remaining 92 to a non-MS group (according to modified ATP III criteria). The serum concentration of sVCAM-1, sE-selectin and sCD40L was determined by commercial solid phase ELISA. The results were expressed as a median and interquartile range. The MS group showed high levels of sVCAM-1 (558.9 ng/ml; 481.3-667.6 ng/ml) compared with the non-MS group (405.2 ng/ml; 361.0-470.5 ng/ml) (p<0.0001). As well, the median level of sCD40L (3.0 ng/ml; 2.1l-11.7 ng/ml) was significantly higher in the MS group than that in the non-MS group (2.6 ng/ml; 2.3-3.4 ng/ml) (p=0.0061). sE-selectin levels did not differ significantly between the groups: 73.9 ng/ml (58.3-87.0 ng/ml) and 68.5 ng/ml (51.6-97.5 ng/ml) in the MS and non-MS group, respectively. In conclusion, the serum levels of sVCAM-1 and sCD40L, but not sE-selectin, were significantly higher in patients with MS than in subjects that did not present MS. MS may therefore increase the expression of cell adhesion molecules, probably through endothelial activation. IntroductionMetabolic syndrome (MS) is a cluster of cardiovascular risk factors including central obesity, hypertension, dyslipidemias and glucose intolerance (1). Clinically, it has reached epidemic proportions, and with an increase in the elderly population its incidence and prevalence will further multiply (2).Visceral adipose tissue, an important feature in individuals with MS, produces a range of circulating molecules with proinflammatory and pro-atherosclerotic actions. Several of these adipokines, including tumour necrosis factor · (TNF-·) and interleukin 6 (IL-6), have been linked to alterations in endothelial functions (3).An alteration that characterizes endothelial dysfunction involves the secretion of cellular adhesion molecules (CAMs) on the surface of endothelial cells (ECs), thus enabling the CAMs to bind leukocytes (4,5). VCAM-1 (vascular cell adhesion molecule-1) is not expressed at high levels on the endothelium, but can be regulated in vitro in response to TNF-·, IL-4 and interferon-Á (IFN-Á) cytokines that are synthesized by adipose as well as other tissues. Soluble VCAM-1 (sVCAM-1) is found in the serum of healthy pe...

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Alterations in cell adhesion molecules and other biomarkers of cardiovascular disease in patients with metabolic syndrome

Cited by 42 publications

References 55 publications

High Sensitivity C-Reactive Protein, Tumor Necrosis Factor-α, Interleukin-6, and Vascular Cell Adhesion Molecule-1 Levels in Asian Indians with Metabolic Syndrome and Insulin Resistance (CURES-105)

High Sensitivity C-Reactive Protein, Tumor Necrosis Factor-α, Interleukin-6, and Vascular Cell Adhesion Molecule-1 Levels in Asian Indians with Metabolic Syndrome and Insulin Resistance (CURES-105)

ProteinO-GlcNAcylation: a new signaling paradigm for the cardiovascular system

Increased concentrations of soluble vascular cell adhesion molecule-1 and soluble CD40L in subjects with metabolic syndrome

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