Chromogranin A (CgA (CHGA)) is the major soluble protein co-stored and co-released with catecholamines and can function as a pro-hormone by giving rise to several bioactive peptides. This review summarizes the physiological functions, the pathogenic implications, and the recent use of these molecules as biomarkers in several pathological conditions. A thorough literature review of the electronic healthcare databases MEDLINE, from January 1985 to September 2013, was conducted to identify articles and studies concerned with CgA and its processing. The search strategies utilized keywords such as chromogranin A, vasostatins 1 and 2, chromofungin, chromacin, pancreastatin, catestatin, WE14, chromostatin, GE25, parastatin, and serpinin and was supplemented by the screening of references from included papers and review articles. A total of 209 English-language, peer-reviewed original articles or reviews were examined. The analysis of the retrospective literature suggested that CgA and its several bioactive fragments exert a broad spectrum of regulatory activities by influencing the endocrine, the cardiovascular, and the immune systems and by affecting the glucose or calcium homeostasis. As some peptides exert similar effects, but others elicit opposite responses, the regulation of the CgA processing is critical to maintain homeostasis, whereas an unbalanced production of peptides that exert opposing effects can have a pathogenic role in several diseases. These clinical implications entail that CgA and its derived peptides are now used as diagnostic and prognostic markers or to monitor the response to pharmacological intervention not only in endocrine tumors, but also in cardiovascular, inflammatory, and neuropsychiatric diseases.
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Maria Angela D'amico, Barbara Ghinassi, Pascal Izzicupo, Lamberto Manzoli, and A Di Baldassarre
Xia Wu, Zhiling Li, Wenjiang Sun, and Huan Zheng
Polycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular disease in women. Hyperhomocysteinemia (H-Hcy) is closely related to arterial stiffness (AS) in patients with cardiovascular disease. This study aimed to investigate the relationship between serum homocysteine(Hcy) level and brachial-ankle pulse wave velocity (baPWV) in Chinese women with PCOS. A total of 124 PCOS women were enrolled and divided into two groups according to their baPWV values: normal, baPWV < 1400 cm/s and high AS, baPWV ≥ 1400 cm/s. Univariate analysis was performed to investigate the relative factors for baPWV, and multiple regression analysis was used to evaluate the association of Hcy with baPWV. The group with high AS (n = 35) had higher Hcy levels than the other group (n = 89; P < 0.05). Moreover, univariate analysis revealed that serum Hcy was positively correlated with baPWV (r = 0.133, P < 0.01). In multiple regression analysis, the age-adjusted serum Hcy level was positively correlated with baPWV (β = 0.201, P < 0.01). It remained positively associated with baPWV (β = 0.145, P < 0.01) after further adjustments for age, BMI, PCOS duration, systolic blood pressure, and homeostasis model assessment-insulin resistance as well as several other factors correlated with baPWV. Our results demonstrated that H-Hcy was significantly and independently related to elevated baPWV, suggesting that Hcy might play a role in the pathologic process of AS in women with PCOS. Further researches with more subjects are needed to explore whether Hcy would be a promising biomarker for the stratification management of PCOS women.
Line K Johnson, Kirsten B Holven, Njord Nordstrand, Jan R Mellembakken, Tom Tanbo, and Jøran Hjelmesæth
We aimed to examine whether a whole-grain crispbread (CB) low-fructose, low-calorie diet (LCD) might be superior to a traditional LCD based on fructose-rich liquid meal replacements (LMRs) with respect to improvement of various cardiometabolic risk factors and reproductive hormones. Parallel-group randomised controlled clinical trial. Morbidly obese women with polycystic ovarian syndrome (PCOS) were randomised to either an 8-week CB-LCD or LMR-LCD (900–1100 kcal/day, fructose 17 g/day or 85 g/day). A total of 51 women completed the study. Body weight, fat mass and waist circumference reduced by mean (s.d.) 10.0 (4.8) kg, 7.4 (4.2) kg and 8.5 (4.4) cm, with no significant differences between groups. Total-cholesterol, HDL-cholesterol and Apo-A1 were significantly reduced within both groups (all P values <0.01), with no significant between-group differences. The triacylglycerol and LDL-cholesterol levels were reduced within the LMR group only, with no significant between-group differences. Blood pressure and most measures of glucose metabolism improved significantly in both diet groups, with no significant between-group difference. Uric acid levels rose by 17.7 (46.4) and 30.6 (71.5) μmol/l in the CB and LMR group, respectively, with no significant difference between groups. Gastrointestinal discomfort was significantly and equally reduced in both intervention groups. Free testosterone index was reduced in both groups, with no significant difference between groups. Morbidly obese women with PCOS who underwent either an 8-week low or high-fructose LCD-diet had similar changes in various cardiometabolic risk factors and reproductive hormones. Registration at ClinicalTrials.gov: NCT00779571.
Antonia Ertelt, Ann-Kristin Barton, Robert R Schmitz, and Heidrun Gehlen
This review summarizes similarities and differences between the metabolic syndromes in humans and equines, concerning the anatomy, symptoms, and pathophysiological mechanisms. In particular, it discusses the structure and distribution of adipose tissue and its specific metabolic pathways. Furthermore, this article provides insights and focuses on issues concerning laminitis in horses and cardiovascular diseases in humans, as well as their overlap.
Trevor Lewis, Eva Zeisig, and Jamie E Gaida
While metabolic health is acknowledged to affect connective tissue structure and function, the mechanisms are unclear. Glucocorticoids are present in almost every cell type throughout the body and control key physiological processes such as energy homeostasis, stress response, inflammatory and immune processes, and cardiovascular function. Glucocorticoid excess manifests as visceral adiposity, dyslipidemia, insulin resistance, and type 2 diabetes. As these metabolic states are also associated with tendinopathy and tendon rupture, it may be that glucocorticoids excess is the link between metabolic health and tendinopathy.
To synthesise current knowledge linking glucocorticoid exposure to tendon structure and function.
Narrative literature review.
We provide an overview of endogenous glucocorticoid production, regulation, and signalling. Next we review the impact that oral glucocorticoid has on risk of tendon rupture and the effect that injected glucocorticoid has on resolution of symptoms. Then we highlight the clinical and mechanistic overlap between tendinopathy and glucocorticoid excess in the areas of visceral adiposity, dyslipidemia, insulin resistance and type 2 diabetes. In these areas, we highlight the role of glucocorticoids and how these hormones might underpin the connection between metabolic health and tendon dysfunction.
There are several plausible pathways through which glucocorticoids might mediate the connection between metabolic health and tendinopathy.
Xiaomei Zhang, Zhangrong Xu, Xingwu Ran, and Linong Ji
Lower extremity arterial disease (LEAD) is highly prevalent in people with diabetes in China, but half of cases are underdiagnosed due to diversities of clinical presentations and complexities of diagnosis approaches. The purpose of this study was to develop a risk score model for LEAD to facilitate early screening among type 2 diabetes (T2DM) patients.
A total of 8313 participants with T2DM from the China DIA-LEAD study, a multicenter, cross-sectional epidemiological study, were selected as the training dataset to develop a risk score model for LEAD by logistic regression. The area under receiver operating characteristic curve (AUC) and bootstrapping were utilized for internal validation. A dataset of 287 participants consecutively enrolled from a teaching hospital between July 2017 and November 2017 was used as external validation for the risk score model.
A total of 931 (11.2%) participants were diagnosed as LEAD in the training dataset. Factors including age, current smoking, duration of diabetes, blood pressure control, low density lipoprotein cholesterol, estimated glomerular filtration rate, and coexistence of cardio and/or cerebrovascular disease correlated with LEAD in logistic regression analysis and resulted in a weighed risk score model of 0–13. A score of ≥5 was found to be the optimal cut-off for discriminating moderate–high risk participants with AUC of 0.786 (95% CI: 0.778–0.795). The bootstrapping validation showed that the AUC was 0.784. Similar performance of the risk score model was observed in the validation dataset with AUC of 0.731 (95% CI: 0.651–0.811). The prevalence of LEAD was 3.4, 12.1, and 27.6% in the low risk (total score 0–4), moderate risk (total score 5–8), and high risk (total score 9–13) groups of LEAD in the training dataset, respectively, which were 4.3, 19.6, and 30.2% in the validation dataset.
The weighed risk score model for LEAD could reliably discriminate the presence of LEAD in Chinese with T2DM aged over 50 years, which may be helpful for a precise risk assessment and early diagnosis of LEAD.
Katica Bajuk Studen and Marija Pfeifer
Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age. Besides hyperandrogenism, oligomenorrhea and fertility issues, it is associated with a high prevalence of metabolic disorders and cardiovascular risk factors. Several genetic polymorphisms have been identified for possible associations with cardiometabolic derangements in PCOS. Different PCOS phenotypes differ significantly in their cardiometabolic risk, which worsens with severity of androgen excess. Due to methodological difficulties, longer time-scale data about cardiovascular morbidity and mortality in PCOS and about possible beneficial effects of different treatment interventions is missing leaving many issues regarding cardiovascular risk unresolved.
Xiuzhen Zhang, Dan Xu, Ping Xu, Shufen Yang, Qingmei Zhang, Yan Wu, and Fengyi Yuan
Metformin has been demonstrated to enhance cardioprotective benefits in type 1 diabetes (T1DM). Although glycemic variability (GV) is associated with increased risk of CVD in diabetes, there is a scarcity of research evaluating the effect of metformin on GV in T1DM.
In the present study, the effects of adjuvant metformin therapy on GV and metabolic control in T1DM were explored.
Patients and methods
A total of 65 adults with T1DM were enrolled and subjected to physical examination, fasting laboratory tests, and continuous glucose monitoring, and subsequently randomized 1:1 to 3 months of 1000–2000 mg metformin daily add-on insulin (MET group, n = 34) or insulin (non-MET group, n = 31). After, baseline measurements were repeated.
The mean amplitude of glycemic excursions was substantially reduced in MET group, compared with non-MET group (–1.58 (–3.35, 0.31) mmol/L vs 1.36 (–1.12, 2.24) mmol/L, P = 0.004). In parallel, the largest amplitude of glycemic excursions (–2.83 (–5.47, –0.06) mmol/L vs 0.45 (–1.29, 4.48) mmol/L, P = 0.004), the s.d. of blood glucose (–0.85 (–1.51, 0.01) mmol/L vs –0.14 (–0.68, 1.21) mmol/L, P = 0.015), and the coefficient of variation (–6.66 (–15.00, 1.50)% vs –1.60 (–6.28, 11.71)%, P = 0.012) all demonstrated improvement in the MET group, compared with the non-MET group. Significant reduction in insulin dose, BMI, and body weight was observed in patients in MET, not those in non-MET group.
Additional metformin therapy improved GV in adults with T1DM, as well as improving body composition and reducing insulin requirement. Hence, metformin as an adjunctive therapy has potential prospects in reducing the CVD risk in patients with T1DM in the long term.
Xiaomin Nie, Yiting Xu, Xiaojing Ma, Yun Shen, Yufei Wang, and Yuqian Bao
A high level of free triiodothyronine (FT3) within the reference range may be a potential metabolic risk marker. However, the relationship between different fat depots and FT3 has remained unclear.
We aimed to explore the relationships between segmental fat distribution and FT3 in euthyroid middle-aged and elderly men and postmenopausal women.
A total of 891 subjects (394 men and 497 women) were enrolled. A bioelectrical impedance analyzer was used to measure total, trunk, arm and leg fat mass (FM) and fat percentage (fat%). The leg fat mass to trunk fat mass ratio (LTR) was calculated to evaluate the relative distribution of leg fat compared with that of trunk fat. Thyroid hormones were measured by electrochemical luminescence immunoassay.
FT3 in men did not change significantly with increases in LTR quartiles, while FT3 in women decreased significantly (P for trend = 0.004). In multivariate linear regression analysis, multiple metabolic and cardiovascular risk factors were adjusted. The LTR was negatively related to FT3 in women (P < 0.05). After further mutual adjustment for trunk fat and leg fat parameters, trunk FM and fat% were positively related to FT3, while leg FM and fat% were negatively related to FT3 in women (all P < 0.05).
In euthyroid postmenopausal women, trunk fat was positively correlated with FT3, whereas leg fat was negatively correlated with FT3. Our findings supported that a high level of FT3 within the reference range was related to adverse fat distribution.
Kristin Godang, Karolina Lundstam, Charlotte Mollerup, Stine Lyngvi Fougner, Ylva Pernow, Jörgen Nordenström, Thord Rosén, Svante Jansson, Mikael Hellström, Jens Bollerslev, Ansgar Heck, and the SIPH Study Group
Mild primary hyperparathyroidism has been associated with increased body fat mass and unfavorable cardiovascular risk factors.
To assess the effect of parathyroidectomy on fat mass, glucose and lipid metabolism.
Design, patients, interventions, main outcome measures
119 patients previously randomized to observation (OBS; n = 58) or parathyroidectomy (PTX; n = 61) within the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, an open randomized multicenter study, were included. Main outcome measures for this study were the differences in fat mass, markers for lipid and glucose metabolism between OBS and PTX 5 years after randomization.
In the OBS group, total cholesterol (Total-C) decreased from mean 5.9 (±1.1) to 5.6 (±1.0) mmol/L (P = 0.037) and LDL cholesterol (LDL-C) decreased from 3.7 (±1.0) to 3.3 (±0.9) mmol/L (P = 0.010). In the PTX group, the Total-C and LDL-C remained unchanged resulting in a significant between-group difference over time (P = 0.013 and P = 0.026, respectively). This difference was driven by patients who started with lipid-lowering medication during the study period (OBS: 5; PTX: 1). There was an increase in trunk fat mass in the OBS group, but no between-group differences over time. Mean 25(OH) vitamin D increased in the PTX group (P < 0.001), but did not change in the OBS group. No difference in parameters of glucose metabolism was detected.
In mild PHPT, the measured metabolic and cardiovascular risk factors were not modified by PTX. Observation seems safe and cardiovascular risk reduction should not be regarded as a separate indication for parathyroidectomy based on the results from this study.