Endothelial Function and Dysfunction

Abstract

The endothelium is an important locus of control of vascular functions, and reasonable but not perfect methods exist for assessing endothelial function in vivo in humans. Endothelial dysfunction in diabetes complicated by micro‐ or macroalbuminuria is generalized, in that it affects many aspects of endothelial function. The close linkage between microalbuminuria and endothelial dysfunction in diabetes is an attractive explanation for the fact that microalbuminuria is a risk marker for atherothrombosis. In type 1 diabetes, endothelial dysfunction precedes and may cause diabetic microangiopathy, but it is not clear whether endothelial dysfunction is a feature of the diabetic state per se . In type 2 diabetes, endothelial function is impaired from the onset of the disease and is strongly related to adverse outcomes. It is not clear whether impaired endothelial function is caused by hyperglycemia or by other factors. Regardless of the presence of diabetes, impaired endothelial function is closely associated with and may contribute to insulin resistance. Endothelial dysfunction in diabetes originates from three main sources. First, hyperglycemia and its immediate biochemical sequelae directly alter endothelial function. Second, hyperglycemia influences endothelial cell functioning indirectly by the synthesis of growth factors, cytokines, and vasoactive agents in other cells. Third, the components of the metabolic syndrome can impair endothelial function.

Microalbuminuria and Risk for Cardiovascular Disease

“…Many cross-sectional and somewhat more limited prospective data indicate that microalbuminuria is associated with many cardiovascular risk factors or risk indicators, such as advanced age, male gender, hypertension, diabetes, smoking, obesity, dyslipidemia (low HDL cholesterol and high triglycerides more clearly so than high LDL cholesterol), and hyperhomocysteinemia (20). At first glance, therefore, the association between microalbuminuria might simply be due to confounding by such risk factors, which might cause both microalbuminuria and atherothrombosis and thus explain their association.…”

“…Therefore, an association of microalbuminuria with generalized endothelial dysfunction, if it exists, could explain why microalbuminuria strongly predicts cardiovascular disease. Indeed, microalbuminuria in type 1 and type 2 diabetes usually is accompanied by endothelial dysfunction with regard to the regulation of hemostasis, fibrinolysis, leukocyte adhesion, and NO synthesis and/or availability, as estimated by plasma levels of endothelial function markers such as von Willebrand factor, tissue-type plasminogen activator, soluble vascular cell adhesion molecule-1, and soluble E-selectin and by endothelium-dependent vasodilation in response to increases in flow or to agonists such as cholinergic agents (20,23). Therefore, endothelial dysfunction in individuals with diabetes and microalbuminuria, at the very least, is extensive.…”

“…Indeed, several studies have shown that endothelial dysfunction precedes and predicts the onset of microalbuminuria in individuals without and with diabetes (20,23). It therefore is tempting to postulate that endothelial dysfunction in microalbuminuria explains why microalbuminuria is a consistent marker of increased risk for atherothrombosis.…”

Clinical Significance of Procalcitonin and C-Reactive Protein in the Prediction of Cardiovascular Complications in Patients With Type 2 Diabetes Mellitus

“…Several hypotheses explain the link between microalbuminuria and CVD. One of them suggests that a dysfunction of the vascular endothelium causes both microalbuminuria and CVD [86,87]. Endothelial impairment can be identified by any change in endothelial characteristics that is inappropriate with regard to the maintenance of organ function.…”

“…Therefore, the association of microalbuminuria with generalized endothelial impairment could explain why microalbuminuria strongly predicts CVD. Indeed, microalbuminuria in type 1 and type 2 diabetes is usually paralleled by endothelial impairment regarding the regulation of hemostasis, fibrinolysis, leukocyte adhesion, and no synthesis and/or availability [86]. Jager et al [88] and Stehouwer et al [89] mentioned that chronic, low-grade inflammation is related to the occurrence and progression of microalbuminuria and with risk for atherothrombotic disease.…”