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Angiogenesis, Metabolism, Endothelial and Platelet Markers in Diabetes and Cardiovascular Disease
A D Blann1, J E Brown2, R Heitmar1
1School of Applied Sciences, Huddersfield University, Huddersfield, United Kingdom.
Insights
Diabetic cardiovascular disease shows more adverse endothelial and angiogenic profiles compared to diabetes or cardiovascular disease alone. This suggests a need for more aggressive treatment strategies for patients with both conditions.
Area of Science:
- Cardiovascular Research
- Metabolic Disease Research
- Biomarker Discovery
Background:
- Diabetes mellitus is a significant risk factor for cardiovascular disease (CVD).
- The pathophysiology of diabetes and CVD involves shared abnormalities in metabolic, endothelial, renal, angiogenic, and platelet systems.
- It is hypothesized that these abnormalities are exacerbated in individuals with co-existing diabetes and CVD.
Purpose of the Study:
- To investigate and compare the levels of specific biomarkers related to angiogenesis, metabolic function, endothelium, and platelets in patients with diabetes alone, CVD alone, and combined diabetic cardiovascular disease.
- To identify potential biomarkers that indicate a more severe pathological state in patients with both diabetes and CVD.
Main Methods:
- Serum or plasma samples were collected from three patient groups: diabetes alone (n=66), CVD alone (n=76), and combined diabetic cardiovascular disease (n=70).
- Levels of angiogenesis markers (angiopoietin 1 and 2, VEGF, endoglin), metabolic markers (sRAGE, leptin, lipocalin-2, interleukin-8, cystatin-C), endothelial markers (von Willebrand factor, endothelial microparticles, soluble E selectin), and platelet markers (platelet microparticles, soluble P selectin) were measured.
- Assays used included ELISA, Luminex, and flow cytometry.
Main Results:
- Vascular endothelial growth factor (VEGF), von Willebrand factor, and endothelial microparticles were significantly higher in the diabetic cardiovascular disease group compared to either the diabetes alone or CVD alone groups.
- Soluble E selectin was elevated in diabetic cardiovascular disease versus diabetes alone.
- Cystatin-C and soluble P selectin were higher in both diabetes and diabetic cardiovascular disease groups compared to the CVD alone group.
Conclusions:
- Certain biomarkers, including angiopoietin 1/2, endoglin, sRAGE, leptin, lipocalin-2, interleukin-8, and cystatin-C, do not effectively differentiate between diabetes, CVD, or their combination.
- Patients with diabetic cardiovascular disease exhibit a more detrimental endothelial (von Willebrand factor, endothelial microparticles) and angiogenic (VEGF) profile.
- These findings support the aggressive targeting of patients with diabetic cardiovascular disease for therapeutic interventions.
Abstract:
Introduction: Diabetes is a leading risk factor for cardiovascular disease (CVD), the pathophysiology of both being linked to metabolic, endothelial, renal, angiogenic and platelet abnormalities. We hypothesised that abnormalities in these systems are more adverse in those whose CVD is compounded by diabetes, compared to those with diabetes or CVD alone. Materials and methods: Serum or plasma from 66 patients with diabetes alone, 76 with CVD alone, and 70 with both diabetes and CVD i.e. diabetic cardiovascular disease, was probed for markers of angiogenesis [angiopoietin 1 and 2, vascular endothelial growth factor (VEGF) and endoglin], metabolic [soluble receptor for advanced glycation products (sRAGE), leptin, lipocalin-2, interleukin-8, and cystatin-C], the endothelium (von Willebrand factor, endothelial microparticles and soluble E selectin)], and the platelet (platelet microparticles and soluble P selectin) by ELISA, Luminex or flow cytometry. Results: VEGF (p = 0.04), von Willebrand factor (p = 0.001) and endothelial microparticles (p = 0.042) were all higher in diabetic cardiovascular disease than in diabetes alone and cardiovascular disease alone. Soluble E selectin was higher in diabetic cardiovascular disease than in diabetes alone (p = 0.045), whilst cystatin-C (p = 0.004) and soluble P selectin (p < 0.001) were higher in diabetes and diabetic cardiovascular disease than in cardiovascular disease alone. There were no differences in angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, or interleukin-8. Conclusion: Angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, interleukin-8, and cystatin-c cannot differentiate diabetes from cardiovascular disease, or both conditions combined. Our data point to a more adverse endothelial (von Willebrand factor, endothelial microparticles), and angiogenic profile (VEGF) in those with diabetic cardiovascular disease, supporting the view that this group should be targeted more aggressively.
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