Thiamine and benfotiamine prevent increased apoptosis in endothelial cells and pericytes cultured in high glucose

Beltramo, Elena; Berrone, Elena; Buttiglieri, Stefano; Porta, Massimo

doi:10.1002/dmrr.470

Cited by 70 publications

(50 citation statements)

References 39 publications

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“…In our models, both cell types reduced their proliferation and increased apoptosis when co-cultured in stable high glucose conditions. This happened also in EC cultured alone, consistently with previous evidence in the literature [23][24][25], while HRP in solo cultures showed neither reduced proliferation nor increased apoptosis, confirming our previous data on low sensitivity of human pericytes to persistently high glucose in comparison with bovine cells [5]. Exposure to intermittent high glucose in the contact model, on the contrary, resulted in decreased proliferation and increased apoptosis in all cases, including HRP alone, consistently with our previous findings that HRP are vulnerable to both downwardly fluctuating glucose levels and intermittent exposure [5].…”

Section: Discussionsupporting

confidence: 92%

Human pericyte–endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment

et al. 2012

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Section: Discussionsupporting

confidence: 92%

Human pericyte–endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment

et al. 2012

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“…High glucose levels, in vitro as well as in vivo, induce pericyte apoptosis [46][47][48][49][50], leading to the well-known alterations of retinal capillaries.…”

Section: Pericyte Loss During Dr: Evidences and Clinical Consequencesmentioning

confidence: 99%

Pericyte Loss in Diabetic Retinopathy: Mechanisms and Consequences

Beltramo

Porta

2013

CMC

259

173

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The onset of diabetic retinopathy is characterized by morphologic alterations of the microvessels, with thickening of the basement membrane, loss of inter-endothelial tight junctions and early and selective loss of pericytes, together with increased vascular permeability, capillary occlusions, microaneurysms and, later, loss of endothelial cells. A key role in the evolution of the disease is played by pericytes, specialized contractile mesenchymal cells of mesodermal origin, that, in capillaries, exert a function similar to smooth muscle cells in larger vessels, regulating vascular tone and perfusion pressure. Thickening of the basement membrane, together with systemic and local hypertension, hyperglycaemia, advanced glycation end-product formation and hypoxia, may disrupt the tight link between pericytes and EC causing pericyte apoptosis, while endothelium, deprived of proliferation control, can give rise to new vessels.Pericyte dropout has great consequences on capillary remodelling and may cause the first abnormalities of the diabetic eye which can be observed clinically. Hyperglycaemia and local hypertension are known to be a direct cause of pericyte apoptosis and dropout, and intracellular biochemical pathways of the glucose metabolites have been explored. However, the exact mechanisms are not yet fully understood and need further clarification in order to develop new effective drugs for the prevention of retinopathy.4

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“…Thus, it blocks several hyperglycemia-induced pathways, one of them being endogenous AGEs and dicarbonyls formation (26). Benfotiamine was shown to prevent experimental diabetic retinopathy (26) and in vitro hyperglycemia-induced endothelial dysfunction (27,28). The effects of benfotiamine on in vivo endothelial function remained unknown.…”

Section: Diabetes Care 29:2064 -2071 2006mentioning

confidence: 99%

Benfotiamine Prevents Macro- and Microvascular Endothelial Dysfunction and Oxidative Stress Following a Meal Rich in Advanced Glycation End Products in Individuals With Type 2 Diabetes

et al. 2006

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OBJECTIVE -Diabetes is characterized by marked postprandial endothelial dysfunction induced by hyperglycemia, hypertriglyceridemia, advanced glycation end products (AGEs), and dicarbonyls (e.g., methylglyoxal [MG]). In vitro hyperglycemia-induced MG formation and endothelial dysfunction could be blocked by benfotiamine, but in vivo effects of benfotiamine on postprandial endothelial dysfunction and MG synthesis have not been investigated in humans until now.RESEARCH DESIGN AND METHODS -Thirteen people with type 2 diabetes were given a heat-processed test meal with a high AGE content (HAGE; 15.100 AGE kU, 580 kcal, 54 g protein, 17 g lipids, and 48 g carbohydrates) before and after a 3-day therapy with benfotiamine (1,050 mg/day). Macrovascular flow-mediated dilatation (FMD) and microvascular reactive hyperemia, along with serum markers of endothelial disfunction (E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1), oxidative stress, AGE, and MG were measured during both test meal days after an overnight fast and then at 2, 4, and 6 h postprandially.RESULTS -The HAGE induced a maximum reactive hyperemia decrease of Ϫ60.0% after 2 h and a maximum FMD impairment of Ϫ35.1% after 4 h, without affecting endotheliumindependent vasodilatation. The effects of HAGE on both FMD and reactive hyperemia were completely prevented by benfotiamine. Serum markers of endothelial dysfunction and oxidative stress, as well as AGE, increased after HAGE. These effects were significantly reduced by benfotiamine.CONCLUSIONS -Our study confirms micro-and macrovascular endothelial dysfunction accompanied by increased oxidative stress following a real-life, heat-processed, AGE-rich meal in individuals with type 2 diabetes and suggests benfotiamine as a potential treatment. Diabetes Care 29:2064 -2071, 2006E ndothelial dysfunction is an early marker of atherosclerosis and accompanies states showing a high cardiovascular risk, such as smoking (1), dyslipidemia (2), arterial hypertension (3), obesity (4), coronary artery disease (5), congestive heart failure (6), and type 1 (7) and type 2 (8) diabetes. Postprandial endothelial dysfunction has been proposed as the link between postprandial dysmetabolism and atherosclerosis (9) and occurs not only in patients with cardiovascular disease (10) or diabetes (11) but even in healthy subjects (12). Distinctive and cumulative (11) effects of hyperglycemia (13) and hypertriglyceridemia (14) on postprandial endothelial dysfunction have been shown. Since the postprandial state covers most of our daytime, interventions aimed at reducing postprandial endothelial dysfunction might play a decisive role in prevention of atherosclerosis. Several therapeutic approaches have been suggested for the treatment of postprandial endothelial dysfunction, including insulin, folic acid, tetrahydrobiopterin, vitamins C and E, and statins (11). These approaches aim at reducing postprandial oxidative stress (vitamins C and E, statins, and partly folic acid), postprandial hyperglycemia (insul...

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Thiamine and benfotiamine prevent increased apoptosis in endothelial cells and pericytes cultured in high glucose

Abstract: Thiamine and benfotiamine correct increased apoptosis due to high glucose in cultured vascular cells. Further elucidations of the mechanisms through which they work could help set the basis for clinical use of this vitamin in the prevention and/or treatment of diabetic microangiopathy.

Cited by 70 publications

References 39 publications

Human pericyte–endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment

Human pericyte–endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment

Pericyte Loss in Diabetic Retinopathy: Mechanisms and Consequences

Benfotiamine Prevents Macro- and Microvascular Endothelial Dysfunction and Oxidative Stress Following a Meal Rich in Advanced Glycation End Products in Individuals With Type 2 Diabetes

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