The anti-atherogenic effects of thiazolidinediones

The thiazolidinediones (TZDs) rosiglitazone (ROS) and pioglitazone (PIO) are insulin-sensitising agents widely used to treat patients with type 2 diabetes mellitus (T2DM). Thiazolidinediones significantly improve glycaemic control in diabetics by reduced fasting glucose, insulin and glycated haemoglobin and they delay the progression of insulin resistance/impaired glucose tolerance into T2DM. It is well recognized that adequate glycaemic control and subsequent amelioration of hyperinsulinaemia and hyperglycaemia can delay the onset of vascular complications. TZDs, however, also have a number of anti-atherogenic effects independent of their influences on glucose and insulin metabolism. They improve lipid profiles, lower blood pressure, have anti-inflammatory properties, improve endothelial function and increase large artery compliance in patients with type 2 diabetes mellitus. When compared to rosiglitazone, pioglitazone has more favourable effects on the lipid profiles of patients with T2DM. The disease preventive actions of TZDs may be the result of their agonistic effects on peroxisome proliferator-activated receptors (PPARs), ligand-activated transcription factors that regulate the expression of numerous genes and affect metabolism and vascular parameters. Thiazolidinediones, provide an effective treatment for populations with insulin resistance which is at high risk of developing cardiovascular disease. This paper discusses the differences between ROS and PIO and explores their anti-atherogenic effects with particular focus on post-menopausal women with type 2 diabetes mellitus

Cardiovascular autonomic dysfunction and oxidative stress induced by fructose overload in an experimental model of hypertension and menopause

Background: Metabolic syndrome is characterized by the association of 3 or more risk factors, including: abdominal obesity associated with an excess of abdominal fat, insulin resistance, type 2 diabetes, dyslipidemia and hypertension. Moreover, the prevalence of hypertension and metabolic dysfunctions sharply increases after the menopause. However, the mechanisms involved in these changes are not well understood. Thus, the aim of this study was to assess the effects of fructose overload on cardiovascular autonomic modulation, inflammation and cardiac oxidative stress in an experimental model of hypertension and menopause. Methods: Female SHR rats were divided into (n = 8/group): hypertensive (H), hypertensive ovariectomized (HO) and hypertensive ovariectomized undergoing fructose overload (100 g/L in drinking water) (FHO). Arterial pressure (AP) signals were directly recorded. Cardiac autonomic modulation was evaluated by spectral analysis. Oxidative stress was evaluated in cardiac tissue. Results: AP was higher in the FHO group when compared to the other groups. Fructose overload promoted an increase in body and fat weight, triglyceride concentration and a reduction in insulin sensitivity. IL-10 was reduced in the FHO group when compared to the H group. TNF-α was higher in the FHO when compared to all other groups. Lipoperoxidation was higher and glutathione redox balance was reduced in the FHO group when compared to other groups, an indication of increased oxidative stress. A negative correlation was found between IL-10 and adipose tissue. Conclusion: Fructose overload promoted an impairment in cardiac autonomic modulation associated with inflammation and oxidative stress in hypertensive rats undergoing ovarian hormone deprivation.Fil: Conti, Filipe Fernandes. Universidad Nove de Julho; BrasilFil: Brito, Janaina de Oliveira. Universidad Nove de Julho; BrasilFil: Bernardes, Nathalia. Universidade de Sao Paulo; BrasilFil: Dias, Danielle da Silva. Universidad Nove de Julho; BrasilFil: Sanches, Iris Callado. Universidad Nove de Julho; BrasilFil: Malfitano, Christiane. Universidad Nove de Julho; BrasilFil: Llesuy, Susana Francisca. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Irigoyen, Maria-Claudia. Universidade de Sao Paulo; BrasilFil: De Angelis, Kátia. Universidad Nove de Julho; Brasi

Association between serum Mg2+ concentrations and cardiovascular organ damage in a cohort of adult subjects

Magnesium (Mg2+) levels are associated with insulin resistance, hypertension, atherosclerosis, and type 2 diabetes (T2DM). We evaluated the clinical utility of physiological Mg2+ in assessing subclinical cardiovascular organ damage including increased carotid artery intima-media thickness (c-IMT) and left ventricular mass index (LVMI) in a cohort of well-characterized adult non-diabetic individuals. Age-and gender-adjusted correlations between Mg2+ and metabolic parameters showed that Mg2+ circulating levels were correlated negatively with body mass index (BMI), fasting glucose, and 2h-oral glucose tolerance test (OGTT) glucose. Similarly, Mg2+ levels were significantly and negatively related to c-IMT and LVMI. A multivariate regression analysis revealed that age (β = 0.440; p < 0.0001), BMI (β = 0.225; p < 0.0001), and Mg2+ concentration (β = −0.122; p < 0.01) were independently associated with c-IMT. Age (β = 0.244; p = 0.012), Mg2+ (β = −0.177; p = 0.019), and diastolic blood pressure (β = 0.184; p = 0.038) were significantly associated with LVMI in women, while age (β = 0.211; p = 0.019), Mg2+ (β = −0.171; p = 0.038) and the homeostasis model assessment index of insulin resistance (HOMA-IR) (β = −0.211; p = 0.041) were the sole variables associated with LVMI in men. In conclusion, our data support the hypothesis that the assessment of Mg2+ as part of the initial work-up might help unravel the presence of subclinical organ damage in subjects at increased risk of cardiovascular complications

Circulating Levels of Proprotein Convertase Subtilisin/Kexin Type 9 and Arterial Stiffness in a Large Population Sample: Data From the Brisighella Heart Study

Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulating levels are significantly associated with an increased risk of cardiovascular events. This study aimed to evaluate the relationship between circulating levels of PCSK9 and arterial stiffness, an early instrumental biomarker of cardiovascular disease risk, in a large sample of overall healthy participants

Effects of exercise modalities on arterial stiffness and wave reflection: a systematic review and meta-analysis of randomized controlled trials

Background and Objectives: Physical activity is associated with lower cardiovascular and all-cause mortality. However, the effects of different exercise modalities on arterial stiffness are currently unclear. Our objectives were to investigate the effects of exercise modalities (aerobic, resistance or combined) on pulse wave velocity (PWV) and augmentation index (AIx), and to determine whether the effects on these indices differed according to the participants' or exercise characteristics. Methods: We searched the Medline, Embase and Cochrane Library databases from inception until April 2014 for randomized controlled trials lasting ≥4 weeks investigating the effects of exercise modalities on PWV and AIx in adults aged ≥18 years. Results: Forty-two studies (1627 participants) were included in this analysis. Aerobic exercise improved both PWV (WMD: −0.63 m/s, 95% CI: −0.90, −0.35) and AIx (WMD:−2.63%, 95% CI: −5.25 to −0.02) significantly. Aerobic exercise training showed significantly greater reduction in brachial-ankle (WMD: −1.01 m/s, 95% CI: −1.57, −0.44) than in carotid-femoral (WMD: -0.39 m/s, 95% CI: −0.52, −0.27) PWV. Higher aerobic exercise intensity was associated with larger reductions in AIx (β: −1.55%, CI −3.09, 0.0001). In addition, aerobic exercise had a significantly larger effect in reducing PWV (WMD:−1.0 m/s, 95% CI: −1.43, −0.57) in participants with stiffer arteries (PWV ≥8 m/s). Resistance exercise had no effect on PWV and AIx. There was no significant effect of combined exercise on PWV and AIx. Conclusions: We conclude that aerobic exercise improved arterial stiffness significantly and that the effect was enhanced with higher aerobic exercise intensity and in participants with greater arterial stiffness at baseline. Trial Registration PROSPERO: Database registration: CRD42014009744,

The Metabolic Syndrome among Postmenopausal Women in Gorgan

In this study, we aimed to assess levels of serum 25-hydroxyvitamin D in relation to metabolic syndrome among postmenopausal women in Gorgan. The study group included 100 postmenopausal women who were referred to the different Health Centers in Gorgan. Body mass index, waist circumference, Hip, waist to hip ratio, diastolic blood pressure, triglyceride, fasting blood glucose and 25-hydroxyvitamin D levels were significantly higher in postmenopausal women with metabolic syndrome, but HDL-cholesterol was lower. Prevalence of the metabolic syndrome was 31%. There were significant differences in 25-hydroxy vitamin D of postmenopausal women with and without vitamin D deficiency. Prevalence of the vitamin D deficiency in postmenopausal women was 30%. There were significant differences in 25-hydroxy vitamin D of postmenopausal women with and without vitamin D deficiency who had metabolic syndrome. Our results show that postmenopausal status might be a predictor of metabolic syndrome in this area. Our findings suggested that vitamin D levels have no association with metabolic syndrome. There were no significant differences in vitamin D levels in postmenopausal women with and without metabolic syndrome. Vitamin D deficiency is not associated with the metabolic syndrome

Estrogen, angiogenesis, immunity and cell metabolism: Solving the puzzle

Estrogen plays an important role in the regulation of cardiovascular physiology and the immune system by inducing direct effects on multiple cell types including immune and vascular cells. Sex steroid hormones are implicated in cardiovascular protection, including endothelial healing in case of arterial injury and collateral vessel formation in ischemic tissue. Estrogen can exert potent modulation effects at all levels of the innate and adaptive immune systems. Their action is mediated by interaction with classical estrogen receptors (ERs), ER\u3b1 and ER\u3b2, as well as the more recently identified G-protein coupled receptor 30/G-protein estrogen receptor 1 (GPER1), via both genomic and non-genomic mechanisms. Emerging data from the literature suggest that estrogen deficiency in menopause is associated with an increased potential for an unresolved inflammatory status. In this review, we provide an overview through the puzzle pieces of how 17\u3b2-estradiol can influence the cardiovascular and immune systems

Relationships Between Chemoreflex Responses, Sleep Quality, and Hematocrit in Andean Men and Women.

Andean highlanders are challenged by chronic hypoxia and many exhibit elevated hematocrit (Hct) and blunted ventilation compared to other high-altitude populations. While many Andeans develop Chronic Mountain Sickness (CMS) and excessive erythrocytosis, Hct varies markedly within Andean men and women and may be driven by individual differences in ventilatory control and/or sleep events which exacerbate hypoxemia. To test this hypothesis, we quantified relationships between resting ventilation and ventilatory chemoreflexes, sleep desaturation, breathing disturbance, and Hct in Andean men and women. Ventilatory measures were made in 109 individuals (n = 63 men; n = 46 women), and sleep measures in 45 of these participants (n = 22 men; n = 23 women). In both men and women, high Hct was associated with low daytime SpO2 (p < 0.001 and p < 0.002, respectively) and decreased sleep SpO2 (mean, nadir, and time <80%; all p < 0.02). In men, high Hct was also associated with increased end-tidal PCO2 (p < 0.009). While ventilatory responses to hypoxia and hypercapnia did not predict Hct, decreased hypoxic ventilatory responses were associated with lower daytime SpO2 in men (p < 0.01) and women (p < 0.009) and with lower nadir sleep SpO2 in women (p < 0.02). Decreased ventilatory responses to CO2 were associated with more time below 80% SpO2 during sleep in men (p < 0.05). The obstructive apnea index and apnea-hypopnea index also predicted Hct and CMS scores in men after accounting for age, BMI, and SpO2 during sleep. Finally, heart rate response to hypoxia was lower in men with higher Hct (p < 0.0001). These data support the idea that hypoventilation and decreased ventilatory sensitivity to hypoxia are associated with decreased day time and nighttime SpO2 levels that may exacerbate the stimulus for erythropoiesis in Andean men and women. However, interventional and longitudinal studies are required to establish the causal relationships between these associations