Dysfunction In Metabolic Syndrome Research Articles

STUDY OF THYROID DYSFUNCTION IN PATIENTS WITH METABOLIC SYNDROME

Introduction:
 Metabolic syndrome (MS) is described as insulin resistance, clusters of abnormalities including abdominal obesity, hypertension, hyperglycaemia, increased triglycerides, and decreased high-density lipoprotein cholesterol (HDL-C). In maintaining thermogenesis and metabolic homeostasis Thyroxine and Triidothryronine play an important role. Thyroid is established by thyroid stimulation hormone (TSH). Thyroid hormones up-regulate metabolic pathways relevant to resting energy expenditure, hence obesity and thyroid functions are often correlated. It is still not clear whether these alterations in thyroid hormones are a cause or an effect of obesity. Hypothyroidism is well known to cause diastolic hypertension, endothelial dysfunction, hyperlipidemia and cardiovascular disease. The functions of thyroid affect the components of metabolic syndrome including triglycerides (TG), HDL–cholesterol (HDL-C), blood pressure and plasma glucose. The impact of various degree of thyroid dysfunction on components of metabolic syndrome, however, continues to be debatable. On components of metabolic syndrome, Thyroid dysfunction is also risk factor for ASCVD mediated by the effects of thyroid hormones on glucose metabolism, lipid and blood pressure. In India about onethird of the urban population in large cities has metabolic syndrome with the overall prevalence varying between 11% and 56%. Worldwide Thyroid diseases are most prevalent endocrine disorders. According to various studies it showed that about 42 million people in India suffer from thyroid diseases.
 Aim: The main aim of this study was to study thyroid dysfunction in metabolic syndrome.
 Material and Methods: In this study 150 patients with different age group from 20 years to 60 years old were included with metabolic syndrome diagnosed as per IDF criteria. From all the patients who visit hospital as OPD and IPD patients’ detailed history was recorded and also laboratory examination were done.
 Result: In this study total 150 patients with metabolic syndrome were included in which there were 82 were males and 68 were females. In this study there were maximum numbers of male patients in comparing with female patients as 43.3% and 54.7% respectively with different age group from 20 years to 60 years old. Out of total patients age group of 35 to 50 years old shows maximum and the age group 50- 60 years old showed least as 37% and 23% respectively. In this study in the age group of 35-50 had abnormal TGL values, compared to the other age groups. While HDL values were low in the 50-60 age group compared to others.
 Conclusion: Thyroid dysfunction is common in metabolic syndrome patients. The prevalence of hypothyroidism is more common in metabolic syndrome. Therefore early detection and thyroxine replacement could reduce the significant cardiovascular risk. However, there is still a controversy whether the patients with subclinical hypothyroidism would be benefited from thyroxine replacement. Hence Subclinical hypothyroidism should be picked up and treated at the earliest.
 Keywords: Metabolic syndrome, Thyroid dysfunction, hypothyroidism, HDL

Prevalence of Left Ventricular Diastolic Dysfunction in Metabolic Syndrome as Assessed by Echocardiography

Prevalence of Left Ventricular Diastolic Dysfunction in Metabolic Syndrome as Assessed by Echocardiography

The effect of dicarbonyl stress on the development of kidney dysfunction in metabolic syndrome \u2013 a transcriptomic and proteomic approach

Background and aimsDicarbonyl stress plays an important role in the pathogenesis of microvascular complications that precede the formation of advanced glycation end products, and contributes to the development of renal dysfunction. In renal cells, toxic metabolites like methylglyoxal lead to mitochondrial dysfunction and protein structure modifications.In our study, we investigated the effect of methylglyoxal on metabolic, transcriptomic, metabolomic and proteomic profiles in the context of the development of kidney impairment in the model of metabolic syndrome.Materials and methodsDicarbonyl stress was induced by intragastric administration of methylglyoxal (0.5 mg/kg bw for 4 weeks) in a strain of hereditary hypertriglyceridaemic rats with insulin resistance and fatty liver.ResultsMethylglyoxal administration aggravated glucose intolerance (AUC0–120p < 0.05), and increased plasma glucose (p < 0.01) and insulin (p < 0.05). Compared to controls, methylglyoxal-treated rats exhibited microalbuminuria (p < 0.01). Targeted proteomic analysis revealed increases in urinary secretion of pro-inflammatory parameters (MCP-1, IL-6, IL-8), specific collagen IV fragments and extracellular matrix proteins. Urine metabolomic biomarkers in methylglyoxal-treated rats were mainly associated with impairment of membrane phospholipids (8-isoprostane, 4-hydroxynonenal).Decreased levels of glutathione (p < 0.01) together with diminished activity of glutathione-dependent antioxidant enzymes contributed to oxidative and dicarbonyl stress. Methylglyoxal administration elevated glyoxalase 1 expression (p < 0.05), involved in methylglyoxal degradation. Based on comparative transcriptomic analysis of the kidney cortex, 96 genes were identified as differentially expressed (FDR < 0.05). Network analysis revealed an over-representation of genes related to oxidative stress and pro-inflammatory signalling pathways as well as an inhibition of angiogenesis suggesting its contribution to renal fibrosis.ConclusionOur results support the hypothesis that dicarbonyl stress plays a key role in renal microvascular complications. At the transcriptome level, methylglyoxal activated oxidative and pro-inflammatory pathways and inhibited angiogenesis. These effects were further supported by the results of urinary proteomic and metabolomic analyses.

Pulmonary vascular dysfunction in metabolic syndrome

Metabolic syndrome is a critically important precursor to the onset of many diseases, such as cardiovascular disease, and cardiovascular disease is the leading cause of death worldwide. The primary risk factors of metabolic syndrome include hyperglycaemia, abdominal obesity, dyslipidaemia, and high blood pressure. It has been well documented that metabolic syndrome alters vascular endothelial and smooth muscle cell functions in the heart, brain, kidney and peripheral vessels. However, there is less information available regarding how metabolic syndrome can affect pulmonary vascular function and ultimately increase an individual's risk of developing various pulmonary vascular diseases, such as pulmonary hypertension. Here, we review in detail how metabolic syndrome affects pulmonary vascular function.

Abnormal Microcirculation and Red Blood Cell Function as a Cardiovascular Risk Factor in Metabolic Syndrome

The metabolic syndrome is a highly prevalent condition associated with increased cardiovascular risk in the population. Microvasculature is the terminal part of the cardiovascular system which primarily reacts to the increased secretion of the pro inflammatory adipokines typical for the metabolic syndrome. Microcirculation and blood cell abnormalities are the leading mechanisms of cardiovascular events development in this condition. Prevalence of microcirculation abnormalities and red blood cell dysfunction in metabolic syndrome and their role in the increased blood viscosity and cardiovascular events development are covered by the paper. The microcirculation abnormalities with a special focus on red blood cell dysfunction (impaired aggregation, stiffness) seen in metabolic syndrome and associated conditions are discussed in detail. The impact of abnormal red blood cell deformability (secondary to cholesterol accumulation in the cellular membranes) on the hemorheological abnormalities is revealed. Abnormal red blood cell surface charge due to proinflammatory changes associated with insulin resistance in diabetes mellitus is highlighted. These abnormalities lead to increased red blood cell aggregation and plasma viscosity that are the essential components of cardiovascular events pathogenesis. Their timely diagnosis is crucial for effective cardiovascular prevention.

A single systemic injection of AAV9-hIGFBP2 prevents left ventricular hypertrophy and dysfunction in metabolic syndrome

Metabolic syndrome (MetS) is a known risk factor for cardiovascular events. It is characterized by central obesity plus any two of dyslipidemia, insulin resistance, and hypertension. Obese and diabetic patients with MetS have low plasma insulin-like growth factor binding protein 2 (IGFBP2). Our first aim was to investigate IGFBP2 cardiac expression in MetS patients and in a mice model of MetS. The second aim was to assess if gene therapy with adeno-associated virus 9 carrying human IGFBP2 (AAV9-hIGFBP2) could reduce MetS associated left ventricular hypertrophy in mice. We measured plasma IGFBP2 by ELISA and cardiac mRNA IGFBP2 expression in MetS patients by RT-qPCR. Both plasma levels and heart expression of IGFBP2 were decreased in patients with MetS vs. control patients. Further, in a C57BL/6J mouse model of diet-induced MetS, found similar left ventricular mRNA IGFBP2 expression. Finally, we demonstrated for the first time that in MetS mice with decreased cardiac IGFBP2 mRNA levels, human IGFBP2 can be induced by a single AAV9-hIGFBP2 injection, and that the increased IGFBP2 prevents left ventricle wall thickening, hypertrophy and dysfunction. Human plasma and cardiac IGFBP2 are decreased in MetS patients. In mice, restoration of cardiac IGFBP2 expression level prevents MetS associated left ventricular dysfunction and hypertrophy. These clinical and animal data suggest that IGFBP2 is a new cardiac marker and therapeutic target in MetS to prevent heart remodeling consistent with heart failure.

Aortic dysfunction in metabolic syndrome mediated by perivascular adipose tissue TNFα- and NOX2-dependent pathway.

What is the central question of this study? Tumour necrosis factor-α (TNFα) has been shown to impair vascular function, but the impact of thoracic aorta perivascular adipose tissue (tPVAT)-derived TNFα on tPVAT and aortic function in metabolic syndrome is unknown. What is the main finding and its importance? Release of TNFα by tPVAT causes production of reactive oxygen species in tPVAT through activation of an NADPH-oxidase 2 (NOX2)-dependent pathway, activates production of aortic reactive oxygen species and mediates aortic stiffness, potentially through matrix metalloproteinase9 activity. Neutralization of TNFα and/or inhibition of NOX2 blocks the tPVAT-induced impairment of aortic function. These data partly implicate tPVAT NOX2 and TNFα in mediating the vascular pathology of metabolic syndrome. Perivascular adipose tissue (PVAT) is recognized for its vasoactive effects, but it is unclear how metabolic syndrome impacts thoracic aorta (t)PVAT and the subsequent effect on functional and structural aortic stiffness. Thoracic aorta and tPVAT were removed from 16- to 17-week-old lean (LZR, n=16) and obese Zucker rats (OZR, n=16). The OZR presented with aortic endothelial dysfunction, assessed by wire myography, and increased aortic stiffness, assessed by elastic modulus. The OZR tPVAT exudate further exacerbated the endothelial dysfunction, reducing nitric oxide and endothelium-dependent relaxation (P<0.05). Additionally, OZR tPVAT exudate had increased MMP9 activity (P<0.05) and further increased the elastic modulus of the aorta after 72h of co-culture (P<0.05). We found that the observed aortic dysfunction caused by OZR tPVAT was mediated through increased production and release of tumour necrosis factor-α (TNFα; P<0.01), which was dependent on tPVAT NADPH-oxidase 2 (NOX2) activity. The OZR tPVAT release of reactive oxygen species and subsequent aortic dysfunction were inhibited by TNFα neutralization and/or inhibition of NOX2. Additionally, we found that OZR tPVAT had reduced activity of the active sites of the 20S proteasome (P<0.05) and reduced superoxide dismutase activity (P<0.01). In conclusion, metabolic syndrome causes tPVAT dysfunction through an interplay between TNFα and NOX2 that leads to tPVAT-mediated aortic stiffness by activation of aortic reactive oxygen species and increased MMP9 activity.

Predictors of Left Ventricular Diastolic Dysfunction in Metabolic Syndrome: Gender Differences

Predictors of Left Ventricular Diastolic Dysfunction in Metabolic Syndrome: Gender Differences

Comparative Study of Nitric Oxide Levels in Metabolic Syndrome and Diabetes Mellitus Patients

The metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for cardiovascular disease and type 2 diabetes (DM). A proposed central event in metabolic syndrome is a decrease in the amount of bioavailable nitric oxide (NO) from endothelial NO synthase (eNOS). Patients with diabetes invariably show an impairment of endothelium-dependent vasodilation. Our aim is to evaluate the endothelial dysfunction in metabolic syndrome & Diabetes patients by estimation of nitric oxide levels. The study was conducted at SLIMS, Puducherry. The study included 200 diabetic patients, 200 metabolic syndrome patients and 200 Controls. When compared to controls, It was found a significant increase (p<0.001) in nitric oxide among metabolic syndrome and diabetes group and significant difference (p<0.001) between diabetes mellitus and metabolic syndrome groups being higher in metabolic syndrome group. Nitric oxide is reduced in the course of vascular disease in diabetes mellitus. Increased production of superioxide anion on oxidative stress to reduce plasma nitric oxide levels.

Study of thyroid dysfunction in metabolic syndrome and association with its components

BackgroundMetabolic syndrome is a constellation of metabolic derangements such as obesity, insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, hypertension, and a proinflammatory and prothrombotic state. Thyroid dysfunction is common among metabolic syndrome patients. This study investigates association of thyroid dysfunction with components of metabolic syndrome with an aim to establish link between both entities. ObjectivesTo study the spectrum of thyroid dysfunction in patients with metabolic syndrome and to evaluate the association of thyroid dysfunction with components of metabolic syndrome. MethodologyIn this prospective case control study, thyroid profile was estimated in 100 metabolic syndrome patients as well as 100 age/sex matched control population attending OPD and various wards of New Hospital Medical College Kota, over a period of one year. ResultsIn the 100 metabolic syndrome patients included in this study 37% had subclinical hypothyroidism (SCH), 12% had overt hypothyroidism and 2% had overt hyperthyroidism. In control group 8% had SCH and 4% had overt hypothyroidism. Thyroid dysfunction was significantly associated (P=0.025) with high waist circumference in patients with metabolic syndrome. ConclusionThyroid dysfunction particularly subclinical hypothyroidism is a common endocrine abnormality associated with metabolic syndrome patients, more so in female population and elderly and is associated with one component of metabolic syndrome (waist circumference). Hence, thyroid function tests may be included as a routine investigation in all metabolic syndrome patients.

Swimming, but not vitamin E, ameliorates prothrombotic state and hypofibrinolysis in a rat model of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is associated with a systemic procoagulant hypofibrinolysis state that is considered as a risk factor for microangiopathy and peripheral vascular diseases. Swimming exercise ameliorates the metabolic dysfunction in type 2 diabetes. Vitamin E is a natural antioxidant that reduces the risk of endothelial dysfunction in metabolic syndrome. The aim of the present study is to investigate the effect of combined swimming exercise with vitamin E on coagulation as well as blood fibrinolysis markers in rats with NAFLD. Eighty male rats were divided into control, control+vitamin E, control+exercise, high-fat diet (HFD), HFD+vitamin E, HFD+exercise, and HFD+vitamin E+exercise groups. Glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), alanine transaminase (ALT) and aspartate transaminase (AST), intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), endothelin-1, von Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor (PAI-1), fibrin degradation products (FDP), platelet count and aggregation, bleeding and clotting times, activated partial thromboplastin time (aPTT), and prothrombin time (PT) were determined. HFD increased lipid profile, insulin, glucose, HOMA-IR, liver enzymes, adhesion molecules, endothelin-1, vWF, platelet aggregation, fibrinogen, FDP, and PAI-1, and decreased clotting and bleeding times and HDL. Although exercise reduced lipid profile, glucose, insulin, HOMA-IR, vWF, platelet aggregation, fibrinogen, FDP, and PAI-1 and increased PT, aPTT, bleeding and clotting times, and HDL, vitamin E had no effect. Exercise, but not vitamin E, ameliorated the HFD-induced prothrombotic state and enhanced fibrinolytic activity.

Raised TSH is associated with endothelial dysfunction in Metabolic Syndrome: A case control study

Endothelial dysfunction has been considered as one of the important factors in pathogenesis of Metabolic Syndrome (Met S). Subclinical hypothyroidism (SCH) has also been reported to be associated with Met S. The aim of our study is to evaluate the association of raised TSH with mediators of endothelial dysfunction in Met S with Subclinical hypothyroidism as compared to healthy controls. Study population consisted of 100 subjects, out of which 50 were cases of Met S and 50 were healthy controls. Met S group were further divided into two, based on the presence & absence of SCH. Serum insulin, T3, T4, TSH were measured by chemiluminescence based immunoassay (CLIA). Serum nitric oxide (NO) levels were measured by Modified Griess's method and serum endothelin-1 (ET-1) levels were measured by ELISA. Out of 50 cases of Met S, SCH was diagnosed in 22. The mean serum TSH levels were significantly higher in Met S cases as compared to healthy controls (5.7 ± 1.2 μIU/mL vs. 2.3 ± 1.6 μIU/mL, P <0.0001). Mean serum NO levels were significantly lower in Met S cases as compared to healthy control (15.4 ± 10 μM vs. 21 ± 10 μM, p = 0.009). Mean serum ET-1 levels were significantly higher in Met S cases as compared to healthy controls (2.68 ± 1.7 fmol/mL vs. 2.1 ± 0.84 fmol/mL, p = 0.011). On Pearson's correlation analysis, TSH showed positive correlation with ET-1 (r = 0.341, p = 0.001) and negative correlation with NO (r = -0.331, p = 0.001). Binary logistic regression analysis showed that TSH, NO and ET-1 has significant odd's ratio for predicting Met S. Met S cases were screened for thyroid abnormalities and found to have 44% of SCH along with co-existing endothelial dysfunction. Raised TSH in SCH could cause endothelial dysfunction which may lead to Met S and associated co-morbidities. Present study gives new insight in linking endothelial dysfunction and raised TSH in Met S. Therefore, Met S cases should be screened for SCH and treated appropriately to attenuate endothelial dysfunction and associated comorbidities in Met S.

Cerebral microvascular dysfunction in metabolic syndrome is exacerbated by ischemia\u2013reperfusion injury

BackgroundMetabolic syndrome (MetS) is associated with an increased risk of cerebrovascular diseases, including cerebral ischemia. Microvascular dysfunction is an important feature underlying the pathophysiology of cerebrovascular diseases. In this study, we aimed to investigate the impacts of ischemia and reperfusion (IR) injury on the cerebral microvascular function of rats with high-fat diet-induced MetS.ResultsWe examined Wistar rats fed a high-fat diet (HFD) or normal diet (CTL) for 20 weeks underwent 30 min of bilateral carotid artery occlusion followed by 1 h of reperfusion (IR) or sham surgery. Microvascular blood flow was evaluated on the parietal cortex surface through a cranial window by laser speckle contrast imaging, functional capillary density, endothelial function and endothelial–leukocyte interactions by intravital videomicroscopy. Lipid peroxidation was assessed by TBARs analysis, the expression of oxidative enzymes and inflammatory markers in the brain tissue was analyzed by real-time PCR. The cerebral IR in MetS animals induced a functional capillary rarefaction (HFD IR 117 ± 17 vs. CTL IR 224 ± 35 capillary/mm2; p < 0.05), blunted the endothelial response to acetylcholine (HFD IR −16.93% vs. CTL IR 16.19% from baseline inner diameter p < 0.05) and increased the endothelial–leukocyte interactions in the venules in the brain. The impact of ischemia on the cerebral microvascular blood flow was worsened in MetS animals, with a marked reduction of cerebral blood flow, exposing brain tissue to a higher state of hypoxia.ConclusionsOur results demonstrate that during ischemia and reperfusion, animals with MetS are more susceptible to alterations in the cerebral microcirculation involving endothelial dysfunction and oxidative stress events.

Proinflammatory Cytokines are Soluble Mediators Linked with Ventricular Arrhythmias and Contractile Dysfunction in Metabolic Syndrome

Metabolic syndrome (MS) increases cardiovascular risk and is associated with cardiac dysfunction and arrhythmias, although the precise mechanisms are still under study. Moreover, the proinflammatory cytokines present in MS have emerged as a possible cause of adverse cardiac events. Male Wistar rats fed with 30% sucrose in drinking water and standard chow for 25–27 weeks were compared to a control group. The MS group showed increased weight, visceral fat, blood pressure and serum triglycerides. The most important increases in serum cytokines compared to the control animals, included IL-1β (7-fold increase), TNF-α (84%), IL-6 (41%) and leptin (2-fold), which increase their gene expression (35-fold) in the heart tissue. Heart function ex vivo showed that the MS group had decreased response for mechanical performance under a challenge of isoproterenol (ISO). Importantly, MS hearts under ISO had almost twice the incidence of ventricular fibrillation. Healthy rat cardiomyocytes exposed to MS group serum with increased proinflammatory cytokines showed impairment in cell shortening and Ca2+handling during ISO treatment, slightly decreased cell shortening and Ca2+ transient amplitude (23%), a slowed cytosolic Ca2+ removal (17%) and 7.5-fold more frequent spontaneous Ca2+ release events. These spontaneous contractions can also provide a substrate for ventricular arrhythmias. Our study found that serum proinflammatory mediators in MS contribute to arrhythmic events and are a potential candidate for preventing or reducing the arrhythmogenic patter in obesity and MS.

Impaired endothelium-derived hyperpolarization-type relaxation in superior mesenteric arteries isolated from female Otsuka Long-Evans Tokushima Fatty rats

Endothelium-derived hyperpolarization (EDH) is an important signaling mechanism of endothelium-dependent vasorelaxation, and little attention has been paid to the EDH-type responses in female metabolic syndrome such as that observed with type-2 diabetes. We previously reported that EDH-type relaxation was impaired in superior mesenteric arteries from male Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type-2 diabetes, however, the response was unclear in female OLETF rat. Thus, the aim of this study was to examine if EDH-type relaxation was altered in superior mesenteric arteries isolated from female OLETF rats compared to age-matched, control female Long-Evans Tokushima Otsuka (LETO) rats at age 50–59 weeks. We investigated concentration–relaxation curves for acetylcholine (at age 50–53 weeks), NS309 (an activator of small- and intermediate-conductance calcium-activated potassium channels) (at age 50–53 weeks), and GSK1016790A (an agonist of transient receptor potential vanilloid type 4, TRPV4) (at age 58 or 59 weeks) in the presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine and the cyclooxygenase inhibitor indomethacin to investigate EDH-type responses in the superior mesenteric artery. Obesity, mild hyperglycemia, hyperinsulinemia, and hyperlipidemia (i.e., increased total cholesterol, triglyceride, and non-esterified fatty acids) were more frequent in OLETF rats than in age-matched LETO rats at age 50–53 weeks. Acetylcholine-, NS309-, and GSK1016790A-induced relaxations in arteries from OLETF rats were all significantly reduced compared to those in LETO rats. These results indicated that EDH-type relaxations were impaired in female OLETF rats. This novel experimental model may provide new insights into vascular dysfunction in metabolic syndrome in females.

339 - Changes of mitochondrial dynamic evoked by circulating exosomes are associated to endothelial dysfunction in metabolic syndrome

339 - Changes of mitochondrial dynamic evoked by circulating exosomes are associated to endothelial dysfunction in metabolic syndrome

The Role of Reactive Oxygen Species in the Pathogenesis of Adipocyte Dysfunction in Metabolic Syndrome. Prospects of Pharmacological Correction

It is established that oxidative stress induces insulin resistance of adipocytes, increases secretion leptin, IL-6, TNF-α by adipocytes. Adiponectin secretion by adipocytes is reduced after the action of reactive oxygen species. Metabolic syndrome contributes to oxidative stress in adipose tissue, on the one hand due to the activation of production of reactive oxygen species by adipocyte NADPH-oxidase, and on the other hand by reducing the antioxidant defense adipocytes. It is found that obesity itself can induce oxidative stress. Chronic stress, glucocorticoids, mineralocorticoids, angiotensin-II, TNF-α play an important role in the pathogenesis of oxidative stress of adipocytes. Metformin remains the cure for the treatment of insulin resistance. The positive results in the treatment of metabolic syndrome by losartan were obtained. Antioxidants and flavonoids exhibit a positive impact on the course of the experimental metabolic syndrome.

Cardiovascular function in male and female JCR:LA-cp rats: effect of high-fat/high-sucrose diet.

Thirty percent of the world population is diagnosed with metabolic syndrome. High-fat/high-sucrose (HF/HS) diet (Western diet) correlates with metabolic syndrome prevalence. We characterized effects of the HF/HS diet on vascular (arterial stiffness, vasoreactivity, and coronary collateral development) and cardiac (echocardiography) function, oxidative stress, and inflammation in a rat model of metabolic syndrome (JCR rats). Furthermore, we determined whether male versus female animals were affected differentially by the Western diet. Cardiovascular function in JCR male rats was impaired versus normal Sprague-Dawley (SD) rats. HF/HS diet compromised cardiovascular (dys)function in JCR but not SD male rats. In contrast, cardiovascular function was minimally impaired in JCR female rats on normal chow. However, cardiovascular function in JCR female rats on the HF/HS diet deteriorated to levels comparable to JCR male rats on the HF/HS diet. Similarly, oxidative stress was markedly increased in male but not female JCR rats on normal chow but was equally exacerbated by the HF/HS diet in male and female JCR rats. These results indicate that the Western diet enhances oxidative stress and cardiovascular dysfunction in metabolic syndrome and eliminates the protective effect of female sex on cardiovascular function, implying that both males and females with metabolic syndrome are at equal risk for cardiovascular disease.NEW & NOTEWORTHY Western diet abolished protective effect of sex against cardiovascular disease (CVD) development in premenopausal animals with metabolic syndrome. Western diet accelerates progression of CVD in male and female animals with preexisting metabolic syndrome but not normal animals. Exacerbation of baseline oxidative stress correlates with accelerated progression of CVD in metabolic syndrome animals on Western diet.

Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II.

Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia. Control and MetS rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); and (c) fenofibrate-treated myocardial infarction (MI-F). Treatment with fenofibrate significantly reduced triglycerides, non-high density lipoprotein cholesterol (non-HDL-C), insulin levels and insulin resistance index (HOMA-IR) in MetS animals. MetS and MI increased Ang II concentration and AT1 expression, favored myocardial oxidative stress (high levels of malondialdehyde, overexpression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), decreased total antioxidant capacity and diminished expression of superoxide dismutase (SOD)1, SOD2 and catalase) and inhibited expression of the insulin signaling cascade: phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PkB, also known as Akt)/Glut-4/endothelial nitric oxide synthase (eNOS). In conclusion, fenofibrate treatment favors an antioxidant environment as a consequence of a reduction of the Ang II/AT1/NOX4 signaling pathway, reestablishing the cardiac insulin signaling pathway. This might optimize cardiac metabolism and improve the vasodilator function during myocardial ischemia.

Advances in the non-invasive assessment of vascular dysfunction in metabolic syndrome and diabetes: Focus on endothelium, carotid mechanics and renal vessels

AimThe present paper is a selective review on the methodology and clinical significance of techniques to assess specifically endothelial function, carotid mechanics and renal vascular function, particularly in the light of vascular dysfunction in metabolic syndrome and type 2 diabetes. Data synthesisEndothelial dysfunction appears to be earlier detectable in the microcirculation of patients with altered glucose metabolism, while it attains significance in the macrocirculation at more advanced disease stages. Smooth muscle cell dysfunction is now increasingly recognized to play a role both in the development of endothelial dysfunction and abnormal arterial distensibility. Furthermore, impaired glucose metabolism affects carotid mechanics through medial calcification, structural changes in extracellular matrix due to advanced glycation and modification of the collagen/elastin material stiffness. The assessment of renal vascular function by dynamic ultrasound or magnetic resonance imaging has recently emerged as an appealing target for identifying subtle vascular alterations responsible for the development of diabetic nephropathy. ConclusionsVascular dysfunction represents a major mechanism for the development of cardiovascular disease in patients with abnormal glucose metabolism. Hence, the currently available non-invasive techniques to assess early structural and vascular abnormalities merit recommendation in this population, although their predictive value and sensitivity to monitor treatment-induced changes have not yet been established and are still under investigation.