Plasma Levels of Cellular Fibronectin in Diabetes

Abstract

Plasma Levels of Cellular Fibronectin in DiabetesOBJECTIVE -Cellular fibronectin is an endothelium-derived protein involved in subendothelial matrix assembly. Elevated plasma levels of cellular fibronectin therefore reflect loss of endothelial cell polarization or injury to blood vessels. Consequently, elevated plasma levels of circulating cellular fibronectin have been described in clinical syndromes with vascular damage, although not in diabetes or atherosclerosis.RESEARCH DESIGN AND METHODS -We determined fibronectin levels in 52 patients with type 1 diabetes, 50 patients with type 2 diabetes, 54 patients with a history of ischemic stroke, 23 patients with renal artery stenosis, and 64 healthy subjects.RESULTS -Circulating cellular fibronectin was significantly elevated in patients with diabetes (4.3 ± 2.8 µg/ml) compared with patients with ischemic stroke (2.0 ± 0.9 µg/ml), patients with renovascular hypertension (1.7 ± 1.1 µg/ml), and healthy subjects (1.4 ± 0.6 µg/ml). Patients with diabetes and at least one cardiovascular risk factor had an almost 2.5-fold increase in cellular fibronectin compared with diabetic subjects without such a risk factor. In multivariate regression analysis, higher triglycerides, current or past cigarette smoking, and higher urinary albumin excretion were independently associated with an increase in circulating cellular fibronectin in diabetes.CONCLUSIONS -These results suggest that circulating cellular fibronectin may be a marker protein for endothelial cell activation, especially in diabetes. Prospective studies are needed to explore this possibility.

Levels of extra domain A containing fibronectin in human atherosclerotic plaques are associated with a stable plaque phenotype

“…This may explain why EDA is not released from the arterial wall during atherosclerosis. However, in diabetic patients EDA is released from the vessel wall into the circulation and EDA levels are associated with diabetes [8]. EDA is involved in many other processes and disorders related to pathophysiological circumstances in the vessel wall [4][5][6][7][8][9][10][11][12][13].…”

“…Fibronectin containing EDA was measured with an enzyme-linked immunosorbent assay (ELISA) developed at the University Medical Center Utrecht [8]. Microtiter plates were coated overnight with IgG 1 monoclonal antibody IST-9 (1.06 g/mL) directed against Extra domain A of fibronectin (Abcam, Cambridge, UK) in carbonate buffer (Na 2 CO 3 15 mM, NaHCO 3 35 mM, pH 9.6) at 4 • C. Wells were washed with PBS/0.1% Tween and then blocked with phosphate-buffered saline (PBS)/3% bovine serum albumin (BSA)/0.1% Tween.…”

“…Expression of fibronectin containing EDA is increased in pathophysiological conditions, for example, in graft versus host disease leading to fibrosis of the skin, fibrosis in lung, liver and kidney, diabetes, rheumatoid arthritis, cardiac transplantation, vascular intimal proliferation and vascular hypertension [4][5][6][7][8][9][10][11][12][13].…”

Plasma Fibronectin Concentration in Obese/Overweight Pregnant Women: A Possible Risk Factor for Preeclampsia

“…Changes in the concentration of fibronectin in tissues and body fluids have been reported in various disease conditions. For example elevated levels of fibronectin have been found in plasma of patients with rheumatoid vasculitis [2], collagen vascular diseases, diabetes mellitus [3], chronic obstructive pulmonary disease [4], ischemic heart disease [5], renal cancer [6], gastrointestinal cancer [7], acute myocardiac infarction [8], coronary artery disease [9] and trauma [10]. Increased levels of fibronectin in plasma of patients with some of these conditions were attributed to increased synthesis caused by proinflammatory cytokines, and release of extracelluar matrix and cell surface fibronectins into circulating plasma [3].…”

Serum fibronectin content in the patients suffering from type 1 diabetes mellitus with microangiopathies since the childhood and in the subjects presenting with obesity

“…Накопление белков в субэндотелиальном матриксе при СД вы-является при микроскопии в виде Шифф-ПРОБЛЕМЫ ЭНДОКРИНОЛОГИИ, 1,2015 положительных веществ, содержащих ламинин, коллаген IV типа, фибронектин [9]. Таким образом, содержание фибронектина в плазме может отобра-жать изменения экстрацелюлярного матрикса и по-ражение сосудистой стенки при СД.…”