34 results on '"Saxton, Sophie N."'
Search Results
2. The Role of Perivascular Adipose Tissue in Arterial Function in Health and Disease
- Author
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Agabiti-Rosei, Claudia, Barp, Clarissa, Saxton, Sophie N., Heagerty, Anthony M., Mancia, Giuseppe, Series Editor, Agabiti-Rosei, Enrico, Series Editor, Heagerty, Anthony M., editor, and Rizzoni, Damiano, editor
- Published
- 2020
- Full Text
- View/download PDF
3. Time-restricted feeding: a free and effective method of managing hypertension by ameliorating inflammation?
- Author
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Almansoor, Zahra R. and Saxton, Sophie N.
- Published
- 2022
- Full Text
- View/download PDF
4. Emerging Roles of Sympathetic Nerves and Inflammation in Perivascular Adipose Tissue
- Author
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Saxton, Sophie N., Withers, Sarah B., and Heagerty, Anthony M.
- Published
- 2019
- Full Text
- View/download PDF
5. Influence of Perivascular Adipose Tissue on Microcirculation: A Link Between Hypertension and Obesity.
- Author
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Agabiti-Rosei, Claudia, Saxton, Sophie N., De Ciuceis, Carolina, Muiesan, Maria Lorenza, Rizzoni, Damiano, Agabiti Rosei, Enrico, and Heagerty, Anthony M.
- Abstract
Alterations in microcirculation play a crucial role in the pathogenesis of cardiovascular and metabolic disorders such as obesity and hypertension. The small resistance arteries of these patients show a typical remodeling, as indicated by an increase of media or total wall thickness to lumen diameter ratio that impairs organ flow reserve. The majority of blood vessels are surrounded by a fat depot which is termed perivascular adipose tissue (PVAT). In recent years, data from several studies have indicated that PVAT is an endocrine organ that can produce a variety of adipokines and cytokines, which may participate in the regulation of vascular tone, and the secretory profile varies with adipocyte phenotype and disease status. The PVAT of lean humans largely secretes the vasodilator adiponectin, which will act in a paracrine fashion to reduce peripheral resistance and improve nutrient uptake into tissues, thereby protecting against the development of hypertension and diabetes. In obesity, PVAT becomes enlarged and inflamed, and the bioavailability of adiponectin is reduced. The inevitable consequence is a rise in peripheral resistance with higher blood pressure. The interrelationship between obesity and hypertension could be explained, at least in part, by a cross-talk between microcirculation and PVAT. In this article, we propose an integrated pathophysiological approach of this relationship, in order to better clarify its role in obesity and hypertension, as the basis for effective and specific prevention and treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. Perivascular Adipose Tissue Anticontractile Function Is Mediated by Both Endothelial and Neuronal Nitric Oxide Synthase Isoforms.
- Author
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Saxton, Sophie N., Withers, Sarah B., and Heagerty, Anthony M.
- Subjects
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NITRIC-oxide synthases , *ADIPOSE tissues , *ELECTRIC stimulation , *VASCULAR resistance - Abstract
Background: The mechanism of the perivascular adipose tissue (PVAT) anticontractile effect is well characterized in rodent visceral vascular beds; however, little is known about the mechanism of PVAT anticontractile function in subcutaneous vessels. In addition, we have previously shown that PVAT anticontractile function is nitric oxide synthase (NOS) dependent but have not investigated the roles of NOS isoforms. Objective: Here, we examined PVAT anticontractile function in the mouse gracilis artery, a subcutaneous fat depot, in lean control and obese mice and investigated the mechanism in comparison to a visceral depot. Method: Using the wire myograph, we generated responses to noradrenaline and electrical field stimulation in the presence of pharmacological tools targeting components of the known PVAT anticontractile mechanism. In addition, we performed ex vivo "fat transplants" in the organ bath. Results: The mechanism of PVAT anticontractile function is similar between subcutaneous and visceral PVAT depots. Both endothelial and neuronal NOS isoforms mediated the PVAT anticontractile effect. Loss of PVAT anticontractile function in obesity is independent of impaired vasoreactivity, and function can be restored in visceral PVAT by NOS activation. Conclusions: Targeting NOS isoforms may be useful in restoring PVAT anticontractile function in obesity, ameliorating increased vascular tone, and disease. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
7. Perivascular Adipose Tissue Contributes to the Modulation of Vascular Tone in vivo
- Author
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Saxton, Sophie N., Withers, Sarah B., Nyvad, Jakob, Mazur, Aleksandra, Matchkov, Vladimir, Heagerty, Anthony M., Aalkjaer, Christian, Saxton, Sophie N., Withers, Sarah B., Nyvad, Jakob, Mazur, Aleksandra, Matchkov, Vladimir, Heagerty, Anthony M., and Aalkjaer, Christian
- Abstract
Background: Perivascular adipose tissue (PVAT) reduces vascular tone in isolated arteries in vitro, however there are no studies of PVAT effects on vascular tone in vivo. In vitro adipocyte beta(3)-adrenoceptors play a role in PVAT function via secretion of the vasodilator adiponectin. Objective: We have investigated the effects of PVAT on vessel diameter in vivo, and the contributions of beta(3)-adrenoceptors and adiponectin. Method: In anaesthetised rats, sections of the intact mesenteric bed were visualised and the diameter of arteries was recorded. Arteries were stimulated with electrical field stimulation (EFS), noradrenaline (NA), arginine-vasopressin (AVP), and acetylcholine (Ach). Results: We report that in vivo, stimulation of PVAT with EFS, NA, and AVP evokes a local anti-constrictive effect on the artery, whilst PVAT exerts a pro-contractile effect on arteries subjected to Ach. The anti-constrictive effect of PVAT stimulated with EFS and NA was significantly reduced using beta(3)-adrenoceptor inhibition, and activation of beta(3)-adrenoceptors potentiated the anti-constrictive effect of vessels stimulated with EFS, NA, and AVP. The beta(3)-adrenoceptor agonist had no effect on mesenteric arteries with PVAT removed. A blocking peptide for adiponectin receptor 1 polyclonal antibody reduced the PVAT anti-constrictive effect in arteries stimulated with EFS and NA, indicating that adiponectin may be the anti-constrictive factor released upon beta(3)-adrenoceptor activation. Conclusions: These results clearly demonstrate that PVAT plays a paracrine role in regulating local vascular tone in vivo, and therefore may contribute to the modulation of blood pressure. This effect is mediated via adipocyte beta(3)-adrenoceptors, which may trigger release of the vasodilator adiponectin
- Published
- 2019
8. Interleukin-33 rescues perivascular adipose tissue anticontractile function in obesity.
- Author
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Saxton, Sophie N., Whitley, Alice S., Potter, Ryan J., Withers, Sarah B., Grencis, Richard, and Heagerty, Anthony M.
- Subjects
- *
ADIPOSE tissues , *TYPE 2 diabetes , *INTERLEUKIN-33 , *BLOOD sugar , *BLOOD pressure - Abstract
Perivascular adipose tissue (PVAT) depots are metabolically active and play a major vasodilator role in healthy lean individuals. In obesity, they become inflamed and eosinophil-depleted and the anticontractile function is lost with the development of diabetes and hypertension. Moreover, eosinophil-deficient ΔdblGATA-1 mice lack PVAT anticontractile function and exhibit hypertension. Here, we have investigated the effects of inducing eosinophilia on PVAT function in health and obesity. Control, obese, and ΔdblGATA-1 mice were administered intraperitoneal injections of interleukin-33 (IL-33) for 5 days. Conscious restrained blood pressure was measured, and blood was collected for glucose and plasma measurements. Wire myography was used to assess the contractility of mesenteric resistance arteries. IL-33 injections induced a hypereosinophilic phenotype. Obese animals had significant elevations in blood pressure, blood glucose, and plasma insulin, which were normalized with IL-33. Blood glucose and insulin levels were also lowered in lean treated mice. In arteries from control mice, PVAT exerted an anticontractile effect on the vessels, which was enhanced with IL-33 treatment. In obese mice, loss of PVAT anticontractile function was rescued by IL-33. Exogenous application of IL-33 to isolated arteries induced a rapidly decaying endothelium-dependent vasodilation. The therapeutic effects were not seen in IL-33-treated ΔdblGATA-1 mice, thereby confirming that the eosinophil is crucial. In conclusion, IL-33 treatment restored PVAT anticontractile function in obesity and reversed development of hypertension, hyperglycemia, and hyperinsulinemia. These data suggest that targeting eosinophil numbers in PVAT offers a novel approach to the treatment of hypertension and type 2 diabetes in obesity. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
9. Perivascular Adipose Tissue Contributes to the Modulation of Vascular Tone in vivo.
- Author
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Saxton, Sophie N., Withers, Sarah B., Nyvad, Jakob, Mazur, Aleksandra, Matchkov, Vladimir, Heagerty, Anthony M., and Aalkjær, Christian
- Subjects
- *
ADIPOSE tissues , *MESENTERIC artery , *BLOOD pressure , *PEPTIDE receptors , *ADIPONECTIN , *CONTRACTILE proteins - Abstract
Background: Perivascular adipose tissue (PVAT) reduces vascular tone in isolated arteries in vitro, however there are no studies of PVAT effects on vascular tone in vivo. In vitro adipocyte β3-adrenoceptors play a role in PVAT function via secretion of the vasodilator adiponectin. Objective: We have investigated the effects of PVAT on vessel diameter in vivo, and the contributions of β3-adrenoceptors and adiponectin. Method: In anaesthetised rats, sections of the intact mesenteric bed were visualised and the diameter of arteries was recorded. Arteries were stimulated with electrical field stimulation (EFS), noradrenaline (NA), arginine-vasopressin (AVP), and acetylcholine (Ach). Results: We report that in vivo, stimulation of PVAT with EFS, NA, and AVP evokes a local anti-constrictive effect on the artery, whilst PVAT exerts a pro-contractile effect on arteries subjected to Ach. The anti-constrictive effect of PVAT stimulated with EFS and NA was significantly reduced using β3-adrenoceptor inhibition, and activation of β3-adrenoceptors potentiated the anti-constrictive effect of vessels stimulated with EFS, NA, and AVP. The β3-adrenoceptor agonist had no effect on mesenteric arteries with PVAT removed. A blocking peptide for adiponectin receptor 1 polyclonal antibody reduced the PVAT anti-constrictive effect in arteries stimulated with EFS and NA, indicating that adiponectin may be the anti-constrictive factor released upon β3-adrenoceptor activation. Conclusions: These results clearly demonstrate that PVAT plays a paracrine role in regulating local vascular tone in vivo, and therefore may contribute to the modulation of blood pressure. This effect is mediated via adipocyte β3-adrenoceptors, which may trigger release of the vasodilator adiponectin. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
10. MECHANISTIC LINKS BETWEEN OBESITY, DIABETES, AND BLOOD PRESSURE: ROLE OF PERIVASCULAR ADIPOSE TISSUE.
- Author
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Saxton, Sophie N., Clark, Ben J., Withers, Sarah B., Eringa, Etto C., and Heagerty, Anthony M.
- Subjects
- *
BLOOD pressure , *ADIPOSE tissues , *ADIPOSE tissue diseases , *OBESITY , *FAT cells , *CELL populations - Abstract
Obesity is increasingly prevalent and is associated with substantial cardiovascular risk. Adipose tissue distribution and morphology play a key role in determining the degree of adverse effects, and a key factor in the disease process appears to be the inflammatory cell population in adipose tissue. Healthy adipose tissue secretes a number of vasoactive adipokines and anti-inflammatory cytokines, and changes to this secretory profile will contribute to pathogenesis in obesity. In this review, we discuss the links between adipokine dysregulation and the development of hypertension and diabetes and explore the potential for manipulating adipose tissue morphology and its immune cell population to improve cardiovascular health in obesity. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
11. β3 -Adrenoceptor stimulation of perivascular adipocytes leads to increased fat cell-derived NO and vascular relaxation in small arteries.
- Author
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Bussey, Charlotte E., Withers, Sarah B., Saxton, Sophie N., Bodagh, Neil, Aldous, Robert G., and Heagerty, Anthony M.
- Subjects
ADRENERGIC receptors ,FAT cells ,NORADRENALINE ,ADIPOSE tissues ,WESTERN immunoblotting ,ARTERIAL physiology ,ADRENERGIC beta agonists ,ANIMAL experimentation ,ARTERIES ,BLOOD vessels ,VASODILATION ,CELL receptors ,CELLULAR signal transduction ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,MEMBRANE proteins ,NITRIC oxide ,POTASSIUM ,RATS ,RESEARCH ,EVALUATION research ,ADIPONECTIN ,PHARMACODYNAMICS - Abstract
Background and Purpose: In response to noradrenaline, healthy perivascular adipose tissue (PVAT) exerts an anticontractile effect on adjacent small arterial tissue. Organ bath solution transfer experiments have demonstrated the release of PVAT-derived relaxing factors that mediate this function. The present studies were designed to investigate the mechanism responsible for the noradrenaline-induced PVAT anticontractile effect.Experimental Approach: In vitro rat small arterial contractile function was assessed using wire myography in the presence and absence of PVAT and the effects of sympathomimetic stimulation on the PVAT environment explored using Western blotting and assays of organ bath buffer.Key Results: PVAT elicited an anticontractile effect in response to noradrenaline but not phenylephrine stimulation. In arteries surrounded by intact PVAT, the β3 -adrenoceptor agonist, CL-316243, reduced the vasoconstrictor effect of phenylephrine but not noradrenaline. Kv 7 channel inhibition using XE 991 reversed the noradrenaline-induced anticontractile effect in exogenously applied PVAT studies. Adrenergic stimulation of PVAT with noradrenaline and CL-316243, but not phenylephrine, was associated with increased adipocyte-derived NO production, and the contractile response to noradrenaline was augmented following incubation of exogenous PVAT with L-NMMA. PVAT from eNOS-/- mice had no anticontractile effect. Assays of adipocyte cAMP demonstrated an increase with noradrenaline stimulation implicating Gαs signalling in this process.Conclusions and Implications: We have shown that adipocyte-located β3 -adrenoceptor stimulation leads to activation of Gαs signalling pathways with increased cAMP and the release of adipocyte-derived NO. This process is dependent upon Kv 7 channel function. We conclude that adipocyte-derived NO plays a central role in anticontractile activity when rodent PVAT is stimulated by noradrenaline. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
12. Role of Sympathetic Nerves and Adipocyte Catecholamine Uptake in the Vasorelaxant Function of Perivascular Adipose Tissue.
- Author
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Saxton, Sophie N., Ryding, Katie E., Aldous, Robert G., Withers, Sarah B., Ohanian, Jacqueline, and Heagerty, Anthony M.
- Published
- 2018
- Full Text
- View/download PDF
13. PS-B04-6: FIBROBLAST GROWTH FACTOR 21 - A POTENTIAL NEW TREATMENT FOR HYPERTENSION?
- Author
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Williamson, Hannah M, Heagerty, Anthony M, and Saxton, Sophie N
- Published
- 2023
- Full Text
- View/download PDF
14. Chronic vagal nerve stimulation has no effect on tachycardia‐induced heart failure progression or excitation–contraction coupling.
- Author
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Radcliffe, Emma J., Pearman, Charles M., Watkins, Amy, Lawless, Michael, Kirkwood, Graeme J., Saxton, Sophie N., Eisner, David A., and Trafford, Andrew W.
- Subjects
NEURAL stimulation ,HEART failure ,VAGAL tone ,HEART beat ,SYMPTOMS ,HAIR follicles ,ATRIOVENTRICULAR node - Abstract
Autonomic dysregulation plays a key role in the development and progression of heart failure (HF). Vagal nerve stimulation (VNS) may be a promising therapeutic approach. However, the outcomes from clinical trials evaluating VNS in HF have been mixed, and the mechanisms underlying this treatment remain poorly understood. Intermittent high‐frequency VNS (pulse width 300 µs, 30 Hz stimulation, 30 s on, and 300 s off) was used in healthy sheep and sheep in which established HF had been induced by 4 weeks rapid ventricular pacing to assess (a) the effects of VNS on intrinsic cardiac vagal tone, (b) whether VNS delays the progression of established HF, and (c) whether high‐frequency VNS affects the regulation of cardiomyocyte calcium handling in health and disease. VNS had no effect on resting heart rate or intrinsic vagal tone in the healthy heart. Although fewer VNS‐treated animals showed subjective signs of heart failure at 6 weeks, overall VNS did not slow the progression of clinical or echocardiographic signs of HF. Chronic VNS did not affect left ventricular cardiomyocyte calcium handling in healthy sheep. Rapid ventricular pacing decreased the L‐type calcium current and calcium transient amplitude, but chronic VNS did not rescue dysfunctional calcium handling. Overall, high‐frequency VNS did not prevent progression of established HF or influence cellular excitation–contraction coupling. However, a different model of HF or selection of different stimulation parameters may have yielded different results. These results highlight the need for greater insight into VNS dosing and parameter selection and a deeper understanding of its physiological effects. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
15. Personalizing Hypertension Treatment?
- Author
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Withers, Sarah B., Saxton, Sophie N., and Heagerty, Anthony M.
- Abstract
The article focuses on a research on personalize prognostic tools or disease-centered tool to assess cardiovascular risk factors , how vascular remodeling is associated with hypertension and the study of risk factors with the help media-to-lumen ratios in patients.
- Published
- 2018
- Full Text
- View/download PDF
16. Recent updates on the influence of iron and magnesium on vascular, renal, and adipose inflammation and possible consequences for hypertension.
- Author
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Connolly BJ and Saxton SN
- Subjects
- Humans, Animals, Blood Pressure drug effects, Hypertension drug therapy, Hypertension physiopathology, Magnesium, Adipose Tissue metabolism, Inflammation, Iron metabolism, Kidney
- Abstract
The inflammatory status of the kidneys, vasculature, and perivascular adipose tissue (PVAT) has a significant influence on blood pressure and hypertension. Numerous micronutrients play an influential role in hypertension-driving inflammatory processes, and recent reports have provided bases for potential targeted modulation of these micronutrients to reduce hypertension. Iron overload in adipose tissue macrophages and adipocytes engenders an inflammatory environment and may contribute to impaired anticontractile signalling, and thus a treatment such as chelation therapy may hold a key to reducing blood pressure. Similarly, magnesium intake has proven to greatly influence inflammatory signalling and concurrent hypertension in both healthy animals and in a model for chronic kidney disease, demonstrating its potential clinical utility. These findings highlight the importance of further research to determine the efficacy of micronutrient-targeted treatments for the amelioration of hypertension and their potential translation into clinical application., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
- Full Text
- View/download PDF
17. β 3 -Adrenoceptor stimulation of perivascular adipocytes leads to increased fat cell-derived NO and vascular relaxation in small arteries.
- Author
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Bussey CE, Withers SB, Saxton SN, Bodagh N, Aldous RG, and Heagerty AM
- Subjects
- Adipocytes metabolism, Adiponectin metabolism, Animals, Arteries physiology, Blood Vessels metabolism, GTP-Binding Protein alpha Subunits, Gs metabolism, Male, Nitric Oxide biosynthesis, Norepinephrine pharmacology, Potassium Channels agonists, Rats, Rats, Sprague-Dawley, Signal Transduction, Adipocytes drug effects, Adrenergic beta-3 Receptor Agonists pharmacology, Arteries drug effects, Blood Vessels cytology, Nitric Oxide metabolism, Receptors, Adrenergic, beta-3 drug effects, Vasodilation drug effects
- Abstract
Background and Purpose: In response to noradrenaline, healthy perivascular adipose tissue (PVAT) exerts an anticontractile effect on adjacent small arterial tissue. Organ bath solution transfer experiments have demonstrated the release of PVAT-derived relaxing factors that mediate this function. The present studies were designed to investigate the mechanism responsible for the noradrenaline-induced PVAT anticontractile effect., Experimental Approach: In vitro rat small arterial contractile function was assessed using wire myography in the presence and absence of PVAT and the effects of sympathomimetic stimulation on the PVAT environment explored using Western blotting and assays of organ bath buffer., Key Results: PVAT elicited an anticontractile effect in response to noradrenaline but not phenylephrine stimulation. In arteries surrounded by intact PVAT, the β
3 -adrenoceptor agonist, CL-316243, reduced the vasoconstrictor effect of phenylephrine but not noradrenaline. Kv 7 channel inhibition using XE 991 reversed the noradrenaline-induced anticontractile effect in exogenously applied PVAT studies. Adrenergic stimulation of PVAT with noradrenaline and CL-316243, but not phenylephrine, was associated with increased adipocyte-derived NO production, and the contractile response to noradrenaline was augmented following incubation of exogenous PVAT with L-NMMA. PVAT from eNOS-/- mice had no anticontractile effect. Assays of adipocyte cAMP demonstrated an increase with noradrenaline stimulation implicating Gαs signalling in this process., Conclusions and Implications: We have shown that adipocyte-located β3 -adrenoceptor stimulation leads to activation of Gαs signalling pathways with increased cAMP and the release of adipocyte-derived NO. This process is dependent upon Kv 7 channel function. We conclude that adipocyte-derived NO plays a central role in anticontractile activity when rodent PVAT is stimulated by noradrenaline., (© 2018 The British Pharmacological Society.)- Published
- 2018
- Full Text
- View/download PDF
18. Mechanisms of adiponectin-associated perivascular function in vascular disease.
- Author
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Withers SB, Bussey CE, Saxton SN, Melrose HM, Watkins AE, and Heagerty AM
- Subjects
- Adipose Tissue physiopathology, Animals, Blood Vessels physiopathology, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 physiopathology, Humans, Metabolic Syndrome metabolism, Metabolic Syndrome physiopathology, Obesity epidemiology, Obesity physiopathology, Obesity therapy, Risk Factors, Vascular Diseases epidemiology, Vascular Diseases physiopathology, Vascular Diseases therapy, Weight Loss, Adiponectin metabolism, Adipose Tissue metabolism, Blood Vessels metabolism, Obesity metabolism, Paracrine Communication, Signal Transduction, Vascular Diseases metabolism
- Abstract
The concept that fat cells could influence the circulation and indeed cardiac function has been in existence for ≥20 years and has gained a wide interest and no less excitement as evidence has accrued to suggest that such effects may be profound enough to explain disease states, such as hypertension and metabolic changes associated with obesity and type II diabetes mellitus. This ATVB in Focus intends to examine our current knowledge in this field, and suggests mechanisms that may be responsible for normal perivascular function and how they become disordered in obesity. There is the tantalizing prospect of developing new therapeutic approaches to keep obese individuals healthy and redesignating type II diabetes mellitus as a vascular disease., (© 2014 American Heart Association, Inc.)
- Published
- 2014
- Full Text
- View/download PDF
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