Serum Hyaluronan Concentration as a Marker of Angiopathy in Patients with Diabetes Mellitus

Abstract

Abstract. Accumulation of hyaluronan (HA) around smooth muscle cells in lesions of atherosclerosis in diabetic patients suggests that this protein plays an important role in diabetic angiopathy. The aim of this study was to determine the correlation between serum HA concentrations and diabetic angiopathy. Diabetic patients treated with or without an oral hypoglycemic agent and/or insulin for at least 1 year were recruited (n = 95). We also included 20 non-diabetic control subjects. We measured serum levels of HA, body mass index (BMI), fasting plasma glucose (FPG), HbA1c, total cholesterol, triglyceride, glycated albumin (GA), high sensitivity CRP (hs-CRP), monocyte chemoattractant protein (MCP)-1 and evaluated diabetes mellitus history, drug use and presence of related complications. Serum HA levels were significantly (P<0.05) higher in diabetic patients (83.6 ± 5.6 ng/ml, mean ± SEM) than in normal subjects (41.7 ± 12 ng/ ml). In diabetic patients, serum HA concentration significantly correlated with FPG, HbA1c, GA, triglyceride and also significantly correlated with BMI, hs-CRP and MCP-1 and tended to be higher in diabetic patients with complications than in those without such complications. Our data suggest that serum HA level correlates with poor blood glucose control and diabetic angiopathy and that it could be used as a marker of diabetic angiopathy. HYALURONAN (HA), the principal CD44 ligand, is synthesized by resident cells of the arterial wall, including endothelial cells, smooth muscle cells, and adventitial fibroblasts and is also abundantly present in the intima and adventitia of all blood vessels. Physiologically, hyaluronan is a multifunctional protein, composed of repeating disaccharides of D-glucuronic acid and N-acetyl-D-glucosamine, and it involved in water and protein homeostasis, cell proliferation, cell locomotion and migration through interactions with its receptor, CD44 [1,2]. Recently, we and others have reported that stimulation of CD44 with mAbs or HA transmits the signal into the cells, which leads to activation of T cells and cytokine or chemokine of release from monocytes/macrophages and synoviocytes [3][4][5]. Recent studies have reported HA production in diabetes-related arterial sclerosis and diabetic nephropathy [6][7][8]. It has been suggested that HA is possibly related to diabetic microangiopathy as well as macroangiopathy. However, there is little information on the correlation between serum HA and diabetes-related vascular disorders.The present study was designed to determine the correlation between serum HA concentrations and some of the components in the metabolic disorders of diabetes and examine the role of HA in predicting the presence of diabetes-related vasculopathies. Methods Study participantsWe studied patients who visited our hospital be-

Low Molecular Weight Hyaluronan Activates Cytosolic Phospholipase A2α and Eicosanoid Production in Monocytes and Macrophages

“…LMW HA increases uptake of oxidized low density lipoprotein into monocytes (63), and HA overproduction promotes atherosclerosis development in the aorta of ApoE-deficient mice (64). Serum HA levels correlate with poor blood glucose control and diabetic angiopathy (65) and are increased in patients with chronic renal failure (66), advanced liver cirrhosis, and in critically ill patients (67). Overproduction of HA is associated with different types of tumors and correlates with malignancy and poor prognosis (68,69).…”

Hyaluronan Synthase 1 (HAS1) Requires Higher Cellular UDP-GlcNAc Concentration than HAS2 and HAS3*

“…Actually, HAS1 expression levels are induced with factors involved in inflammation, like IL-1 ␤ in uterine fibroblasts (46), TGF-␤ in mesothelial cells (9), and prostaglandins in synoviocytes (47), indicating an important role for HAS1 in conditions associated with abnormal glucose metabolism. Serum hyaluronan level is higher in diabetic patients than in healthy subjects and correlates with poor glucose control in the patients (48). Therefore, increased hyaluronan secretion in response to raised glucose levels has been suggested to contribute to diabetic pathologies, including inflammation.…”

NADPH Oxidases Regulate CD44 and Hyaluronic Acid Expression in Thrombin-treated Vascular Smooth Muscle Cells and in Atherosclerosis

“…Furthermore, increased plasma HA levels have been associated with diabetic angiopathy and the susceptibility of diabetic patients to atherosclerosis (48,49). Because the activation of NADPH oxidases contributes to inflammation (50, 51), we investigated soluble CD44 and HA levels in the plasma of apoE Ϫ/Ϫ and apoE…”