Endothelial dysfunction in type 2 diabetes

Natali, Andrea; Ferrannini, Eleuterio

doi:10.1007/s00125-011-2445-5

Cited by 14 publications

(15 citation statements)

References 32 publications

(38 reference statements)

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“…eNOS is a trigger in the delayed preconditioning pathway. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability is present in T2D and the MS [27]. During IR injury, iNOS has a beneficial role in normal myocardium since iNOS knock-out non-diabetic mice show a larger infarct size versus WT-controls [28].…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-converting enzyme inhibition and food restriction restore delayed preconditioning in diabetic mice

Mieren

Nevelsteen

Vanderper

et al. 2013

Cardiovasc Diabetol

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BackgroundClassical and delayed preconditioning are powerful endogenous protection mechanisms against ischemia-reperfusion damage. However, it is still uncertain whether delayed preconditioning can effectively salvage myocardium in patients with co-morbidities, such as diabetes and the metabolic syndrome. We investigated delayed preconditioning in mice models of type II diabetes and the metabolic syndrome and investigated interventions to optimize the preconditioning potential.MethodsHypoxic preconditioning was induced in C57Bl6-mice (WT), leptin deficient ob/ob (model for type II diabetes) and double knock-out (DKO) mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome). Twenty-four hours later, 30 min of regional ischemia was followed by 60 min reperfusion. Left ventricular contractility and infarct size were studied. The effect of 12 weeks food restriction or angiotensin-converting enzyme inhibition (ACE-I) on this was investigated. Differences between groups were analyzed for statistical significance by student’s t-test or one-way ANOVA followed by a Fisher’s LSD post hoc test. Factorial ANOVA was used to determine the interaction term between preconditioning and treatments, followed by a Fisher’s LSD post hoc test. Two-way ANOVA was used to determine the relationship between infarct size and contractility (PRSW). A value of p<0.05 was considered significant.ResultsLeft ventricular contractility is reduced in ob/ob compared with WT and even further reduced in DKO. ACE-I improved contractility in ob/ob and DKO mice. After ischemia/reperfusion without preconditioning, infarct size was larger in DKO and ob/ob versus WT. Hypoxic preconditioning induced a strong protection in WT and a partial protection in ob/ob mice. The preconditioning potential was lost in DKO. Twelve weeks of food restriction or ACE-I restored the preconditioning potential in DKO and improved it in ob/ob.ConclusionDelayed preconditioning is restored by food restriction and ACE-I in case of type II diabetes and the metabolic syndrome.

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Section: Discussionmentioning

confidence: 99%

Angiotensin-converting enzyme inhibition and food restriction restore delayed preconditioning in diabetic mice

Mieren

Nevelsteen

Vanderper

et al. 2013

Cardiovasc Diabetol

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“…It seems likely that the pathogenesis of diabetic vascular disease involves a reduced bioavailability of endothelium-derived nitric oxide [67]. By now it has become clear through human studies that nitric oxide synthase or its bioavailability within the periendothelial environment in type 2 diabetic patients is indeed reduced [68]. …”

Section: Different Pathological Mechanisms In Endothelial Cells Of Hymentioning

confidence: 99%

The Central Role of Endothelial Dysfunction in Cardiorenal Syndrome

2016

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Background: Endothelial dysfunction (ED) has emerged as a critical process in cardiorenal syndrome (CRS). The concept that ED is closely linked with cardiac and renal dysfunction has become an important target for CRS-related research and clinical practice. Summary: The sequence of events leading to ED is initiated by type I endothelial activation (almost immediately) and type II endothelial activation (over hours, days, and even months), followed by endothelial apoptosis and endothelial necrosis. The fact that ED is a continual cellular event divides this process into reversible ED (endothelial activation) and irreversible ED (endothelial apoptosis and necrosis). This basic research-defined concept may have clinical implications. Although most antihypertensive drugs (ACE inhibitors, statins, etc.) are effective in patients with hypertension and diabetes, some of them have proved to be ineffective, which may partly be attributed to irreversible ED. Even though the etiology of ED consists mainly of asymmetric dimethylarginine, nitric oxide, oxidative stress, and anti-endothelial cell antibodies, many other inducers of ED have been identified. In addition, a distinct role of ED has been reported for each type of CRS in humans. Key Messages: Further study is warranted to prove whether ED holds promise as a pharmacological target in CRS patients.

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Section: Introductionmentioning

confidence: 99%

“…However, the mechanisms responsible for the accelerated atherosclerosis observed in T2DM are not yet fully understood [2]. Reduction in the bioavailability of nitric oxide (NO) in the periendothelial environment, which characterizes endothelial dysfunction, is the earliest event in the development of atherosclerosis [2]. Since the occurrence of endothelial dysfunction may be observed before the development of T2DM, it is suggested that these two entities, T2DM and atherosclerosis, may have common pathogenic mechanisms which enhances the possibility of a causal relationship between them [3].…”

Section: Introductionmentioning

confidence: 99%

Dipeptidyl Peptidase 4: A New Link between Diabetes Mellitus and Atherosclerosis?

Júnior

Godoy-Matos

Kraemer‐Aguiar

2015

BioMed Research International

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Type 2 diabetes mellitus (T2DM) has become one of the most prevalent noncommunicable diseases in the past years. It is undoubtedly associated with atherosclerosis and increased risk for cardiovascular diseases. Incretins, which are intestinal peptides secreted during digestion, are able to increase insulin secretion and its impaired function and/or secretion is involved in the pathophysiology of T2DM. Dipeptidyl peptidase 4 (DPP4) is an ubiquitous enzyme that regulates incretins and consequently is related to the pathophysiology of T2DM. DPP4 is mainly secreted by endothelial cells and acts as a regulatory protease for cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function. In T2DM, the activity of DPP4 seems to be increased and there are a growing number of in vitro and in vivo studies suggesting that this enzyme could be a new link between T2DM and atherosclerosis. Gliptins are a new class of pharmaceutical agents that acts by inhibiting DPP4. Thus, it is expected that gliptin represents a new pharmacological approach not only for reducing glycemic levels in T2DM, but also for the prevention and treatment of atherosclerotic cardiovascular disease in diabetic subjects. We aimed to review the evidences that reinforce the associations between DPP4, atherosclerosis, and T2DM.

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Endothelial dysfunction in type 2 diabetes

Cited by 14 publications

References 32 publications

Angiotensin-converting enzyme inhibition and food restriction restore delayed preconditioning in diabetic mice

Angiotensin-converting enzyme inhibition and food restriction restore delayed preconditioning in diabetic mice

The Central Role of Endothelial Dysfunction in Cardiorenal Syndrome

Dipeptidyl Peptidase 4: A New Link between Diabetes Mellitus and Atherosclerosis?

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