Tight Glycemic Control Regulates Fibronectin Expression and Basement Membrane Thickening in Retinal and Glomerular Capillaries of Diabetic Rats
ABSTRACT To determine whether tight glycemic control prevents development of basement membrane (BM) thickening in retinal and glomerular capillaries of diabetic rats and whether the extent to which BM thickening develops is linked to fibronectin (FN) overexpression and the degree of hyperglycemia.
Retinal and renal cortical tissues obtained from the tightly controlled diabetic (TC), poorly controlled diabetic (D), and nondiabetic (N) control rats were subjected to morphometric and biochemical analyses. In both tissues, capillary BM thickening was determined by electron microscopy, and FN protein level was assessed by Western blot analysis. Routine measurements of blood glucose level and glycohemoglobin level were performed throughout the study.
The HbA1c level was significantly increased in D rats, but not in TC rats, compared with those of the N rats with a concomitant increase in capillary BM thickness and FN protein expression in retinal and renal tissues. A strong correlation was observed between retinal and glomerular capillary BM thickness (r=0.79, P=0.0001), between retinal and kidney FN protein levels (r=0.7, P=0.005), between HbA1c and FN protein levels in the retina (r=0.66, P=0.006) and kidney (r= .84, P=0.0003), and between HbA1c level and BM thickness in retinal (r=0.76, P=0.0002) and renal tissues (r=0.64, P=0.004).
In diabetes BM thickening develops in retinal and glomerular capillaries in a correlated manner. Tight glycemic control may be beneficial in preventing the pathologic development of capillary BM thickening and FN overexpression in retinal and renal tissues, two target tissues of diabetic microangiopathy.
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ABSTRACT: Objective Altered subendothelial matrix composition regulates endothelial dysfunction and early atherosclerotic plaque formation. Hyperglycemia promotes endothelial matrix remodeling associated with multiple microvascular complications of diabetes, but a role for altered matrix composition in diabetic atherogenesis has not been described. Therefore, we sought to characterize the alterations in matrix composition during diabetic atherogenesis using both in vitro and in vivo model systems. Methods and Results Streptozotocin-induced diabetes in atherosclerosis-prone ApoE knockout mice promoted transitional matrix expression (fibronectin, thrombospondin-1) and deposition in intima of the aortic arch as determined by qRT-PCR array and immunohistochemistry. Early plaque formation occurs at discrete vascular sites exposed to disturbed blood flow patterns, whereas regions exposed to laminar flow are protected. Consistent with this pattern, hyperglycemia-induced transitional matrix deposition was restricted to regions of disturbed blood flow. Laminar flow significantly blunted high glucose-induced fibronectin expression (mRNA and protein) and fibronectin fibrillogenesis in endothelial cell culture models, whereas high glucose-induced fibronectin deposition was similar between disturbed flow and static conditions. Conclusions Taken together, these data demonstrate that flow patterns and hyperglycemia coordinately regulate subendothelial fibronectin deposition during early atherogenesis.Atherosclerosis 01/2013; 232(2). DOI:10.1016/j.atherosclerosis.2013.11.052 · 3.97 Impact Factor
Conference Paper: Asymptotic capacity of beamforming with limited feedback[Show abstract] [Hide abstract]
ABSTRACT: We study the capacity of a single-user channel with multiple antennas and limited feedback. The receiver has perfect channel knowledge, and can relay B bits, which specify a beamforming vector, to the transmitter. We show that a random vector quantization scheme is asymptotically optimal, and give a simple expression for the associated capacity.Information Theory, 2004. ISIT 2004. Proceedings. International Symposium on; 08/2004
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ABSTRACT: Hyperglycemia is the most prevalent characteristic of diabetes and plays a central role in mediating adverse effects on vascular cells during the progression of diabetic vascular complications. In diabetic microangiopathy, hyperglycemia induces biochemical and molecular changes in microvascular cells that ultimately progress to retinal, renal, and neural complications and extends to other complications, including advanced periodontal disease. In this review, we describe changes involving basement membrane thickening, tissue remodeling, gap junctions, inflammation, cytokines, and transcription factors, and their effects on the pathogenesis of diabetic microvascular complications. The majority of the changes described relate to retinal microangiopathy, since ultrastructural, structural, and biochemical alterations have been well-characterized in this tissue.Journal of dental research 02/2010; 89(2):116-27. DOI:10.1177/0022034509355765 · 4.14 Impact Factor