Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration

Olson, John A.; Whitelaw, Christine Margaret; McHardy, K C; Pearson, David; Forrester, John V.

doi:10.1007/s001250050802

Cited by 87 publications

(82 citation statements)

References 34 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been hypothesised that vascular endothelial growth factor (VEGF), a molecule closely related to the pathogenesis of retinopathy, can trigger early retinal inflammation by inducing the expression and upregulation of sICAM-1 [39]. Increased levels of adhesion molecules, which cause leucocyte adhesion and stasis in the retinal vasculature [40,41], and increased permeability of the endothelium, may be the initial step in the complex pathology of retinopathy [42]. Leucostasis could produce temporary ischaemia upstream and subsequent reperfusion, which may lead to endothelial cell injury and death through the formation of reactive oxygen species [43].…”

Section: Discussionmentioning

confidence: 99%

Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study

et al. 2005

View full text Add to dashboard Cite

Aims/hypothesis: The exact pathogenesis of retinopathy in diabetic and non-diabetic individuals is incompletely understood, but may involve chronic low-grade inflammation and dysfunction of the vascular endothelium. The aim of this study was to investigate the association of inflammation and endothelial dysfunction with prevalent retinopathy in individuals with and without type 2 diabetes. Methods: As part of a population-based cohort study, 625 individuals aged 50-74 years, stratified according to age, sex and glucose tolerance status, underwent an extensive physical examination. Retinopathy was assessed by an ophthalmological examination, including funduscopy and two-field 45°fundus photography with mydriasis in both eyes. Levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), von Willebrand factor, and soluble vascular adhesion molecule-1 (sVCAM-1) were assessed, together with the urinary albumin : creatinine ratio, and the results were combined to obtain summarising z scores for inflammation and endothelial dysfunction. Results: The prevalence of retinopathy was positively associated with tertiles of CRP and sICAM-1. When compared with the lowest tertile, the highest tertile of the inflammatory z score was associated with retinopathy in all subjects (odds ratio [OR]=2.2, 95% CI 1.2-4.1, adjusted for age, sex and glucose tolerance status). The highest tertile of the endothelial dysfunction z score was associated with retinopathy among diabetic individuals (OR=4.4, 95% CI 1.2-15.9, adjusted for age and sex) but not in non-diabetic individuals. Additional adjustment for other risk factors, such as systolic and diastolic blood pressure, BMI, total cholesterol and triglycerides, or mutual adjustment of the inflammatory and endothelial dysfunction z scores did not change the results. Conclusions/interpretation: In this study, inflammatory activity and endothelial dysfunction were associated with retinopathy, which suggests their involvement in the pathogenesis of retinopathy.

show abstract

Section: Discussionmentioning

confidence: 99%

Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study

et al. 2005

View full text Add to dashboard Cite

show abstract

“…19,20 Leucocyte-endothelial interaction (leucocyte rolling and adhesion to the capillary endothelium) is known to have a role in the pathogenesis of DR. [21][22][23] Levels of soluble VCAM-1 in young subjects with Type I diabetes with no evidence of vascular disease seem not to be elevated. 24 Instead, VCAM-1 is increased in diabetic patients with microangiopathy (retinopathy), 25 proliferative retinopathy (PDR) 26,27 and with microalbuminuria and overt nephropathy. 28 In our study, VCAM-1 did not differ between diabetic and normal pregnancy confirming thus a study by Gibson et al (1997) showing that VCAM-1 is not increased abnormally in diabetic women with good glycaemic control during otherwise uncomplicated pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory markers and retinopathy in pregnancies complicated with Type I diabetes

Loukovaara

Immonen

Koistinen

et al. 2004

Eye

View full text Add to dashboard Cite

Aim The relation of maternal cytokine levels to retinopathy progression during diabetic pregnancy is a less studied subject. Therefore, we investigated levels of systemic proinflammatory markers, C-reactive peptide (CRP), interleukin-6 (IL-6) and circulating vascular cell adhesion molecule-1 (VCAM-1) during pregnancy and postpartum in relation to the progression of diabetic retinopathy (DR). Methods A prospective follow-up study of 39 pregnant women with Type I diabetes and eight nondiabetic pregnant women was performed. DR was graded from fundus photographs. Plasma levels of systemic proinflammatory markers were measured by immunofluorometric assay (CRP) and by enzyme-linked immunosorbent assay (IL-6 and VCAM-1) in the first, second (diabetics only), third trimester of pregnancy, and 3 and 6 months postpartum (diabetics only). Results Our diabetic women had good glycaemic control (HbA1c 6.970.8). The levels of IL-6, VCAM-1, and CRP did not differ between diabetic and nondiabetic women throughout pregnancy and postpartum (repeated measures ANOVA between the groups). An association between CRP and progression of retinopathy was observed in diabetic women (P ¼ 0.037). Additional evidence of inter-relationship could be revealed as CRP was higher in those diabetic women with worse glycaemic control (HbA1c) (P ¼ 0.038). Conclusions During pregnancy and postpartum, levels of proinflammatory factors (IL-6, CRP, VCAM-1) seem to be generally similar in Type I diabetic women compared to nondiabetic controls. However, CRP levels were higher in those diabetic women with progression of retinopathy and in those with worse glycaemic control.

show abstract

“…Platelets from diabetic patients are also hyperreactive to in vitro stimulation [4]. Diabetic leucocytes show increased elastase activity [5], enhanced adhesion molecule expression [6] and increased aggregability [7]. Other leucocyte functions, such as cell deformability [8], chemotaxis, and superoxide anion production [9] are also impaired in diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

Exercise-induced platelet and leucocyte activation is not enhanced in well-controlled Type 1 diabetes, despite increased activity at rest

Johansson

Hjemdahl

et al. 2004

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis. Stress can evoke a prothrombotic state with activated platelets and leucocytes, and increased platelet activation at rest has been reported for diabetic subjects. Thus, prothrombotic responses to stress may be enhanced in diabetes mellitus. We therefore evaluated platelet and leucocyte responses to exercise in Type 1 diabetic patients. Methods. Type 1 diabetes mellitus patients with good metabolic control and healthy subjects matched for age and body mass index (n=15 for both) performed a maximal exercise test. Platelet and leucocyte activation and their heterotypic aggregation were monitored by whole blood flow cytometry. Results. Diabetic platelets did not show higher basal levels of P-selectin expression, but were more reactive to ADP and thrombin stimulation. Diabetic patients had increased lymphocyte and monocyte CD11b expression, and increased circulating platelet-monocyte aggregates. Exercise evoked thrombocytosis, increased circulating platelet P-selectin expression, enhanced platelet sensitivity to ADP and thrombin, and elevated plasma levels of soluble P-selectin to a similar degree in diabetic patients and healthy subjects. Exercise induced marked leucocytosis and elevated plasma elastase, but only slightly increased leucocyte CD11b expression and leucocyte reactivity to stimulation by N-formyl-methionyl-leucyl-phenylalanine. In all of these there was no difference between diabetic patients and healthy subjects. The numbers, but not percentages of circulating platelet-leucocyte aggregates were markedly increased by exercise, but the increase was less prominent among diabetic patients. Conclusions/interpretation. Strenuous exercise evokes platelet and leucocyte activation in Type 1 diabetic patients and healthy subjects. Platelet and monocyte hyperactivity were found at rest, but responses to stress were not augmented in metabolically well-controlled Type 1 diabetes mellitus patients.

show abstract

Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration

Cited by 87 publications

References 34 publications

Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study

Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study

Inflammatory markers and retinopathy in pregnancies complicated with Type I diabetes

Exercise-induced platelet and leucocyte activation is not enhanced in well-controlled Type 1 diabetes, despite increased activity at rest

Contact Info

Product

Resources

About