Plasma levels of ICAM-1 and circulating endothelial cells are elevated in unstable types 1 and 2 diabetes

Amine, Mukarram; Sohawon, Schoeb; Lagneau, Louis; Gaham, N.; Berkenboom, Guy; Mols, Pierre; Noordally, S. Oaleed

doi:10.4149/endo_2010_01_17

Cited by 15 publications

(8 citation statements)

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“…Overall, our findings suggest that abnormal endothelium-dependent relaxation and diminished capacity to generate NO in diabetes [19] may result from altered Ca 2+ transients due to impaired NCX and SERCA, which can reduce activation of eNOS and NO production by endothelial cells [38]. Also, altered Ca 2+ transients in diabetic cells may affect ICAM-1-coupled cytoskeletal rearrangements and endothelial cell interactions with inflammatory cells [14], consistent with upregulation of ICAM-1 observed in diabetic patients [22].…”

Section: Discussionsupporting

confidence: 71%

“…Calcium is an important regulator of endothelial function that can mediate each of these pathways, including signaling via NO [12], [13], cell adhesion molecules [14], [15], and receptor tyrosine kinases [16], [17]. Importantly, diabetes is associated with impaired endothelium-dependent relaxation and diminished capacity to generate NO [18]–[21], elevated cell adhesion molecules [22], [23], and decreased angiogenic growth factors [24], [25]. Despite the available evidence of a link between calcium signaling and endothelial cell function, as well as documented endothelial dysfunction in diabetes, the possible effects of diabetes on Ca 2+ signaling in endothelial cells are not known, which may delay the development of vascular therapies for diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

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Diabetes Alters Intracellular Calcium Transients in Cardiac Endothelial Cells

et al. 2012

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Diabetic cardiomyopathy (DCM) is a diabetic complication, which results in myocardial dysfunction independent of other etiological factors. Abnormal intracellular calcium ([Ca2+]i) homeostasis has been implicated in DCM and may precede clinical manifestation. Studies in cardiomyocytes have shown that diabetes results in impaired [Ca2+]i homeostasis due to altered sarcoplasmic reticulum Ca2+ ATPase (SERCA) and sodium-calcium exchanger (NCX) activity. Importantly, altered calcium homeostasis may also be involved in diabetes-associated endothelial dysfunction, including impaired endothelium-dependent relaxation and a diminished capacity to generate nitric oxide (NO), elevated cell adhesion molecules, and decreased angiogenic growth factors. However, the effect of diabetes on Ca2+ regulatory mechanisms in cardiac endothelial cells (CECs) remains unknown. The objective of this study was to determine the effect of diabetes on [Ca2+]i homeostasis in CECs in the rat model (streptozotocin-induced) of DCM. DCM-associated cardiac fibrosis was confirmed using picrosirius red staining of the myocardium. CECs isolated from the myocardium of diabetic and wild-type rats were loaded with Fura-2, and UTP-evoked [Ca2+]i transients were compared under various combinations of SERCA, sarcoplasmic reticulum Ca2+ ATPase (PMCA) and NCX inhibitors. Diabetes resulted in significant alterations in SERCA and NCX activities in CECs during [Ca2+]i sequestration and efflux, respectively, while no difference in PMCA activity between diabetic and wild-type cells was observed. These results improve our understanding of how diabetes affects calcium regulation in CECs, and may contribute to the development of new therapies for DCM treatment.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Diabetes Alters Intracellular Calcium Transients in Cardiac Endothelial Cells

et al. 2012

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“…HbA1c levels correlated with systemic concentrations of the two soluble adhesion molecules. Since both mediators are markers of endothelial dysfunction, increased concentrations may be expected with poor metabolic control [47], [48]. No association was found for insulin dose.…”

Section: Discussionmentioning

confidence: 93%

The Systemic Immune Network in Recent Onset Type 1 Diabetes: Central Role of Interleukin-1 Receptor Antagonist (DIATOR Trial)

et al. 2013

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BackgroundThe hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics.Methods and FindingsAll patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18–39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p<0.05, Spearman correlation) giving rise to a network. Interleukin 1 receptor antagonist (IL1-RA) held a central position and was associated with both pro- and anti-inflammatory mediators. Further central elements were the pro-inflammatory mediators CRP and IL-6, the soluble adhesion molecules sICAM-1 and E-selectin, and MCP-4 which held a central position in the chemokine network. The two Th1-associated mediators IFNγ and IP-10 remained outside the network but correlated with each other. All correlations were positive (r = 0.25–0.72), i.e., high levels of pro-inflammatory mediators were accompanied by increased levels of anti-inflammatory mediators. IL-1RA was the only mediator associated with fasting and liquid mixed meal stimulated C-peptide concentrations (r = 0.31 and 0.24, p = 0.003 and 0.025, after adjustment for age, sex, BMI). There were associations between the immune mediator network and BMI (IL-1RA, CRP, IL-6, MCP-4, MIP-1ß) but few or no associations with HbA1c, insulin dose, lipid parameters, age or sex.ConclusionsIn patients with recent onset type 1 diabetes, systemic acute phase proteins, cytokines, chemokines and soluble adhesion molecules form a network. Among the few central elements IL-1RA has a dominant role. IL-1RA is associated with all other groups of mediators and is the only mediator which correlates (positively) with residual beta cell function.Trial registrationClinicalTrials.gov registration number: NCT00974740

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“…Data from animal studies suggest that experimental diabetes results in impaired endothelium-dependent vasodilation by reduced bioavailability of endothelium-derived nitric oxide 44. El Amine and coauthors reported that endothelial dysfunction is associated with the development of poor glycemic control in people with type 1 and type 2 diabetes mellitus 45. sVCAM-1 has also been shown to be associated with arterial compliance and carotid intima-media thickness in hypertensive patients 46.…”

Section: Discussionmentioning

confidence: 99%

Novel risk factors in long-term hypertension incidence in type 1 diabetes mellitus

Sahakyan

Klein

Myers

et al. 2010

American Heart Journal

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Background-Data from longitudinal studies suggest that biomarkers of inflammation and endothelial dysfunction are associated with development of hypertension. None of these studies have examined the association of these markers with hypertension risk in persons with diabetes. We examined the associations of inflammatory and endothelial dysfunction markers with long-term hypertension incidence in persons with type 1 diabetes mellitus.

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Plasma levels of ICAM-1 and circulating endothelial cells are elevated in unstable types 1 and 2 diabetes

Cited by 15 publications

References 0 publications

Diabetes Alters Intracellular Calcium Transients in Cardiac Endothelial Cells

Diabetes Alters Intracellular Calcium Transients in Cardiac Endothelial Cells

The Systemic Immune Network in Recent Onset Type 1 Diabetes: Central Role of Interleukin-1 Receptor Antagonist (DIATOR Trial)

Novel risk factors in long-term hypertension incidence in type 1 diabetes mellitus

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