The blood vessel, linchpin of diabetic lesions

Plante, Gérard E.; Alfred, Jude; Chakir, M

doi:10.1016/s0026-0495(99)90094-x

Cited by 11 publications

(4 citation statements)

References 21 publications

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“…34 It is likely that such morphological and functional changes on the epithelial luminal membrane is to be associated with alterations in membrane transport proteins, similar to what has been reported in large artery endothelial cell barriers from both the luminal and adventitial (vasa vasorum) sides of these conduit vessels. 35 The highly significant relationship between large artery stiffness and creatinine clearance shown in this review indicates that mostly muscular-elastic, rather than pure muscular, arteries are involved, at least in the early phase of renal functional alterations. 20 Therefore, if a common factor interacts between large muscular-elastic arteries and the kidney, it seems likely that the extracellular matrix of vascular and renal cells should be mainly involved.…”

Section: Hypothesis and Prospective Viewsmentioning

confidence: 80%

Arterial Stiffness and Kidney Function

2004

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Abstract-The vascular hallmark of subjects with end-stage renal disease undergoing hemodialysis is increased aortic stiffness, a phenomenon independent of mean arterial blood pressure, wall stress, and standard cardiovascular risk factors such as plasma glucose, cholesterol, obesity, and smoking. These observations suggest that subtle links might associate arterial stiffness and kidney function in normotensive and hypertensive populations. Recently, aortic pulse wave velocity and creatinine clearance have been shown to be statistically associated in subjects with plasma creatinine Յ130 mol/L, again independently of mean arterial blood pressure and classical cardiovascular risk factors. This association was even shown to predominate in subjects younger than age 55 years. In addition, acceleration of aortic pulse wave velocity with age was more important in these subjects than in untreated normotensive control individuals, and the phenomenon was consistently predicted by baseline plasma creatinine values. Among all antihypertensive drugs, angiotensin-converting enzyme inhibitors only were shown to exhibit a significant and independent effect on aortic stiffness. The use of these drugs was significantly associated with improvement of large aortic stiffness in subjects treated for hypertension. In conclusion, increased stiffness of central arteries is independently associated with reduced creatinine clearance in subjects with mild to severe renal insufficiency, indicating that kidney diseases may interact not only with small but also with large conduit arteries, independently of age, blood pressure level, and classical cardiovascular risk factors. Whether sodium, divalent ionic species (calcium, phosphates), and the renin-angiotensinaldosterone system play a role in such alterations remains to be elucidated. right's disease involves relatively well established links between uremia, high blood pressure, and cardiovascular (CV) complications, which were elegantly described from clinical observations at the end of the 19th century. In those days, biological and imaging tolls were of course quite limited, and exquisite clinical skill was critical for establishing such relationships of unique pathophysiological importance. The tremendous development of renal replacement therapy to handle chronic uremia, including dialysis techniques, over the past half century is associated with an increasing number of CV complications, which are poorly defined at this point in time, illustrating the complex relationships between renal failure and hypertension.Traditionally, one refers easily to three different mechanisms to explain these relationships. First, renal failure is associated with structural and/or functional alterations exclusively located in small resistance arteries. Second, hypertension-related CV complications affecting larger blood vessels of the brain and the heart are related to atherosclerosis, a morbid condition not necessarily immediately and exclusively linked to hypertension. Third, the kidney itself, also a majo...

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Section: Hypothesis and Prospective Viewsmentioning

confidence: 80%

Arterial Stiffness and Kidney Function

2004

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“…19 Increased extravasation of albumin from microvessels is seen in various tissues of diabetic subjects. [3][4][5][6] In rats, vascular hyperpermeability is demonstrated as early as 4 weeks after the onset of STZ-induced diabetes. 20 However, due to the technical limitations, diabetes-induced early functional changes in the coronary microvascular system remain largely unclarified, and even less is known about the permeability property of coronary exchange vessels under hyperglycemic conditions.…”

Section: Discussionmentioning

confidence: 99%

“…1 Characteristic changes in the microcirculation during the early stages of diabetes include autoregulatory dysfunction and increased endothelial permeability. 1,2 Capillary leakage has been documented in various tissues of experimentally diabetic animals, including the retina, 3 aorta, 4 skin, intestine, kidney, 5 and heart. 6 Endothelial barrier dysfunction, occurring before microvascular sclerosis and other structural alterations, is considered to be one of the initiating mechanisms that underlies the pathogenesis of microangiopathic complications.…”

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confidence: 99%

Protein Kinase C Activation Contributes to Microvascular Barrier Dysfunction in the Heart at Early Stages of Diabetes

Yuan¹,

Ustinova²,

Wu³

et al. 2000

Circulation Research

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Abstract-The functional disturbance of microvasculature is recognized as an initiating mechanism that underlies the development of various diabetic complications. Although a causal relationship between microvascular leakage and tissue damage has been well documented in diabetic kidneys and eyes, there is a lack of information regarding the barrier function of coronary exchange vessels in the disease state. The aim of the present study was to evaluate the permeability property of coronary microvessels during the early development of experimental diabetes with a focus on the protein kinase C (PKC)-dependent signaling mechanism. The apparent permeability coefficient of albumin (Pa) was measured in isolated and perfused porcine coronary venules. The administration of high concentrations of D-glucose induced a dose-dependent increase in the Pa value, which was prevented by blockage of PKC with its selective inhibitors bisindolylmaleimide and Goe 6976. More importantly, an elevated basal permeability to albumin was observed in coronary venules at the early onset of streptozotocin-induced diabetes. The hyperpermeability was corrected with bisindolylmaleimide and the selective PKC␤ inhibitor hispidin. Concomitantly, protein kinase assay showed a high PKC activity in isolated diabetic venules. Immunoblot analysis of the diabetic heart revealed a significant subcellular translocation of PKC␤II and PKC⑀ from the cytosol to the membrane, indicating that the specific activity of these isoforms was preferentially elevated. The results suggest that endothelial barrier dysfunction attributed to the activation of PKC occurs at the coronary exchange vessels in early diabetes. (Circ Res. 2000;87:412-417.)Key Words: diabetes Ⅲ microcirculation Ⅲ permeability Ⅲ protein kinases C ardiovascular complications represent the major cause of morbidity and mortality in patients with diabetes mellitus. A functional disturbance in the microvasculature independent of large-vessel atherosclerosis has been implicated in the development of end-organ damage and clinical abnormalities manifested as nephropathy, retinopathy, neuropathy, and skin ulceration. 1 Characteristic changes in the microcirculation during the early stages of diabetes include autoregulatory dysfunction and increased endothelial permeability. 1,2 Capillary leakage has been documented in various tissues of experimentally diabetic animals, including the retina, 3 aorta, 4 skin, intestine, kidney, 5 and heart. 6 Endothelial barrier dysfunction, occurring before microvascular sclerosis and other structural alterations, is considered to be one of the initiating mechanisms that underlies the pathogenesis of microangiopathic complications.The precise cause of vascular hyperpermeability in diabetes has not been established. Recent evidence suggests that hyperglycemia-induced de novo synthesis of diacylglycerol and the subsequent activation of protein kinase C (PKC) constitute an important signaling pathway that leads to endothelial dysfunction. 7,8 The PKC activity has been found to be...

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“…Dysfunction of the vascular endothelium is an early feature of diseases associated with oxidative stress, including atherosclerosis [1, 2], smoking [3], and diabetes [4, 5]. A marker of such dysfunction is increased vascular permeability to serum proteins, leading to tissue edema [6]. Increased permeability to large molecules due to oxidative stress has also been documented at the cellular level.…”

Section: Introductionmentioning

confidence: 99%

Ascorbic acid prevents oxidant‐induced increases in endothelial permeability

May

2010

BioFactors

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Oxidative stress acutely increases the permeability of the vascular endothelium to large molecules that would not otherwise cross the barrier. Ascorbic acid is an antioxidant that tightens the endothelial permeability barrier, so we tested whether it might also prevent the increase in endothelial permeability due to cellular oxidative stress. Treatment of EA.hy926 endothelial cells cultured on filter inserts with H2O2, menadione, and buthionine sulfoximine increased endothelial permeability to radiolabeled inulin. Short-term ascorbate loading of the cells to what are likely physiologic concentrations of the vitamin by treating them with dehydroascorbate prevented the increase in endothelial permeability due to these agents. The non-physiologic antioxidants dithiothreitol and Tempol also prevented increases in endothelial barrier permeability induced by the agents. These results suggest that oxidative stress induced directly by oxidants or indirectly by GSH depletion impairs endothelial barrier function and that intracellular ascorbate may serve to prevent this effect.

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The blood vessel, linchpin of diabetic lesions

Cited by 11 publications

References 21 publications

Arterial Stiffness and Kidney Function

Arterial Stiffness and Kidney Function

Protein Kinase C Activation Contributes to Microvascular Barrier Dysfunction in the Heart at Early Stages of Diabetes

Ascorbic acid prevents oxidant‐induced increases in endothelial permeability

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