Microvascular Dysfunction: A Potential Mechanism in the Pathogenesis of Obesity‐associated Insulin Resistance and Hypertension

Boer, Michiel P. de; Meijer, Rick I.; Wijnstok, Nienke J.; Jonk, Amy M.; Houben, A. J. H. M.; Stehouwer, Coen D. A.; Smulders, Yvo M.; Eringa, Etto C.; Serné, Erik H.

doi:10.1111/j.1549-8719.2011.00130.x

Cited by 128 publications

(108 citation statements)

References 128 publications

(185 reference statements)

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“…Although endothelial dysfunction measured in the skin vasculature correlates well with cardiovascular disease risk in adults 38 and endothelial dysfunction is thought to be a sensitive early marker in adolescence associated with an adverse later cardiovascular phenotype, 9 we cannot be sure what the exact meaning of endothelium-dependent vasodilatation at this young age is and whether the observed associations will track into adulthood. Also, although peripheral vascular endothelial dysfunction is thought to play a role in hypertension and diabetes mellitus, at least in adult obesity, 39 the association between our peripheral vascular measure and endothelial dysfunction in the conduit arteries (the main site of atherosclerosis) in infants is unknown. Finally, we have only studied infant growth, whereas it is clear that childhood growth may also have important effects on later cardiovascular health.…”

Section: Downloaded Frommentioning

confidence: 99%

Influence of Growth During Infancy on Endothelium-Dependent Vasodilatation at the Age of 6 Months

Touwslager

Gerver

Tan³

et al. 2012

Hypertension

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Low birth weight and accelerated infant growth are associated with cardiovascular disease in adulthood. Endothelial dysfunction is regarded as a precursor of atherosclerosis and is also related to infant growth. We aimed to examine whether an association between infant growth and endothelial function is already present during discrete periods of growth during the first 6 months of life in healthy term infants. A cohort of 104 newborns was studied in the first week after birth and reexamined at the age of 6 months. Maximum vasodilatation in response to acetylcholine (endothelium dependent) and nitroprusside (endothelium independent) was measured in the vasculature of the forearm skin, using laser Doppler flowmetry and iontophoresis. Growth was calculated as difference in Z scores for weight, length, weight-for-length, and head circumference. Multivariable multilevel linear regression was used for the analysis. Growth from 0 to 1 month (calculated as difference in weight) was the only window in the first 6 months of life that was significantly and inversely associated with endothelium-dependent vasodilatation at 6 months ( b =−11.72 perfusion units per Z score, P =0.01 in multivariable analysis). Birth size was not important when considered simultaneously with infant growth. Maximum endothelium-independent vasodilatation was not associated with birth size or growth parameters. We conclude that growth in the first month of life is inversely associated with endothelium-dependent vasodilatation at the age of 6 months in healthy term infants, regardless of birth size.

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Section: Downloaded Frommentioning

confidence: 99%

Influence of Growth During Infancy on Endothelium-Dependent Vasodilatation at the Age of 6 Months

Touwslager

Gerver

Tan³

et al. 2012

Hypertension

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“…Systemic microvascular endothelial dysfunction is a key component in the inherent pathogenic complications associated with diseases such as type 2 diabetes, hypertension, and hypercholesterolemia (12,21). Therefore, an independent assessment of the health of the microvasculature in clinical prediabetic populations such as NAFLD is valuable.…”

Section: E54 No-mediated Cutaneous Vasodilator Function In Nafldmentioning

confidence: 99%

“…In support of this, Sokolnicki et al (37) reported no difference in the contribution of NO to cutaneous blood flow during local heating in type 2 diabetic patients and controls of similar age (older individuals) despite differences in BMI being evident between the groups. Clearly, advancing age is an important contributor to microvessel dysfunction and associated CVD risk factors such as hypertension (1,12). Alternatively, the lack of difference in NO microvessel function could be explained by similar lifestyle practices (i.e., sedentary behavior and obesity).…”

Section: E54 No-mediated Cutaneous Vasodilator Function In Nafldmentioning

confidence: 99%

Exercise training improves cutaneous microvascular function in nonalcoholic fatty liver disease

Pugh

Cuthbertson

Sprung

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Pugh CJ, Cuthbertson DJ, Sprung VS, Kemp GJ, Richardson P, Umpleby AM, Green DJ, Cable NT, Jones H. Exercise training improves cutaneous microvascular function in nonalcoholic fatty liver disease. Am J Physiol Endocrinol Metab 305: E50 -E58, 2013. First published May 7, 2013; doi:10.1152/ajpendo.00055.2013.-The leading causes of mortality in nonalcoholic fatty liver disease (NAFLD) relate to cardiovascular disease (CVD). The contribution of nitric oxide (NO) to endothelial function, a surrogate of CVD risk, is currently unknown in NAFLD. We hypothesize that NO-mediated cutaneous microvessel function would be impaired in NAFLD compared with controls and that exercise would enhance microvessel function compared with conventional care. Thirteen NAFLD patients (aged 50 Ϯ 3 yr, BMI 31 Ϯ 1 kg/m 2 ) and seven controls (48 Ϯ 4 yr, 30 Ϯ 2 kg/m 2 ) were studied. NAFLD patients were randomized to either 16 wk of exercise or conventional care. Cutaneous microvessel function was examined using laser Doppler flowmetry combined with intradermal microdialysis of N G -monomethyl-L-arginine to assay the NO dilator response to local forearm heating. Magnetic resonance imaging and spectroscopy quantified abdominal and liver fat, respectively, and cardiorespiratory fitness was assessed. Differences in NO contribution to cutaneous blood flow between NAFLD and control individuals and between interventions were analyzed using general linear modeling. NO contribution to cutaneous blood flow was similar between NAFLD and controls (P ϭ 0.47). Cardiorespiratory fitness was greater following exercise training compared with conventional care. NO contribution to cutaneous blood flow in response to heating at 42°C was 20.4% CVC max (95% CI ϭ 4.4, 36.4) greater following exercise training compared with conventional care (P ϭ 0.02). Exercise training improves cutaneous microvascular NO function in NAFLD patients. The benefit of exercise training compared with conventional care strongly supports a role for exercise in the prevention of CVD in NAFLD. nonalcoholic fatty liver disease; nitric oxide; microvascular function; exercise; exercise training; cutaneous microvessel function NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) is characterized by excess triglyceride accumulation in the liver and is associated with increased liver-related morbidity and mortality. Nevertheless, numerous epidemiological studies have revealed that cardiovascular disease (CVD) accounts for a greater number of deaths than that of liver disease in NAFLD patients (1,30,36), and some report CVD to be the leading cause of mortality (15,30). These findings imply that NAFLD patients are at high risk of cardiovascular events. Endothelial dysfunction, characterized by diminished bioavailability of the antiatherogenic molecule nitric oxide (NO), is the earliest detectable manifestation in the development of atherosclerosis and a strong predictor of future CVD risk in both symptomatic and asymptomatic individuals (17). Although previous cross-sectional studies have shown that NAFLD pati...

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“…These animals lack eNOS mRNA and NOS enzymatic activity, but were fertile and displayed normal anatomy [87,88]. The phenotypic changes caused by eNOS inactivation include lack of endothelium-derived relaxing factor (EDRF) activity and consequent hypertension [87,88], an increase in VSMC proliferation [89], platelet aggregation [90], and in leukocyte-endothelial adhesion [91], abnormalities in mitochondrial function and biogenesis [92], insulin resistance [93], and a higher risk to undergo severe strokes [94] and develop atherosclerosis [95]. Up to our knowledge, CSE/eNOS double knockout (DKO) has not been established.…”

Section: Cse and Enos Knockout Mice Modelsmentioning

confidence: 99%

Hydrogen Sulfide and Endothelial Dysfunction: Relationship with Nitric Oxide

Altaany¹,

Moccia²,

Munaron³

et al. 2014

CMC

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The endothelium is a cellular monolayer that lines the inner surface of blood vessels and plays a central role in the maintenance of cardiovascular homeostasis by controlling platelet aggregation, vascular tone, blood fluidity and fibrinolysis, adhesion and transmigration of inflammatory cells, and angiogenesis. Endothelial dysfunctions are associated with various cardiovascular diseases, including atherosclerosis, hypertension, myocardial infarction, and cardiovascular complications of diabetes. Numerous studies have established the antiinflammatory, anti-apoptotic, and anti-oxidant effects of hydrogen sulfide (H 2 S), the latest member to join the gasotransmitter family along with nitric oxide and carbon monoxide, on vascular endothelium. In addition, H 2 S may prime endothelial cells (ECs) toward angiogenesis and contribute to wound healing, aside to its well-known ability to relax vascular smooth muscle cells (VSMCs), thereby reducing blood pressure. Finally, H 2 S may inhibit VSMC proliferation and platelet aggregation. Consistently, a deficit in H 2 S homeostasis is involved in the pathogenesis of atherosclerosis and of hyperglycaemic endothelial injury. Therefore, the application of H 2 S-releasing drugs or using gene therapy to increase endogenous H 2 S level may help restore endothelial function and antagonize the progression of cardiovascular diseases. The present article reviews recent studies on the role of H 2 S in endothelial homeostasis, under both physiological and pathological conditions, and its putative therapeutic applications. Endothelial structure and functionThe endothelium lines the luminal surface of the entire vascular tree and the cardiac chambers, where it is termed endocardium. As a consequence, the endothelium presents a rather broad extension (300 to 1000 m 2 ) and weight (1.5 kg), achieving sizes comparable to other vital organs of the human body [1,2]. The endothelium can, therefore, be regarded as a real "organ spread across the organism" [3] and, as such, not only it is important for the regulation of local tissue functions, but also for maintaining the whole organism homeostasis [4]. Vascular endothelial cells (ECs) possess a polarized architecture: their luminal membrane is directly exposed to hematic constituents and circulating cells, while the basolateral surface is separated from surrounding tissues by a glycoprotein basement membrane -the sub-endothelial basement -which is formed by fibronectin, laminin, and collagen and is secreted by ECs themselves [2].Heterogeneity is, however, the hallmark of endothelium. ECs differ in morphology, function, and gene expression profile, so that even neighbouring cells from the same organ and blood vessel type exhibit distinct features [4]. For instance, vascular ECs may vary in size, shape, thickness and position of the nucleus. Albeit oriented along direction of blood flow, to attenuate the impact of shear stress forces on the vascular wall, microvascular ECs are rather thin (0.1 µm) and spindle-like, whilst their macrovascul...

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Microvascular Dysfunction: A Potential Mechanism in the Pathogenesis of Obesity‐associated Insulin Resistance and Hypertension

Cited by 128 publications

References 128 publications

Influence of Growth During Infancy on Endothelium-Dependent Vasodilatation at the Age of 6 Months

Influence of Growth During Infancy on Endothelium-Dependent Vasodilatation at the Age of 6 Months

Exercise training improves cutaneous microvascular function in nonalcoholic fatty liver disease

Hydrogen Sulfide and Endothelial Dysfunction: Relationship with Nitric Oxide

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