Application of Metabolomics to Renal and Cardiometabolic Diseases

Author(s):  
Casey M. Rebholz ◽  
Eugene P. Rhee
2018 ◽  
Vol 25 (13) ◽  
pp. 1480-1500 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Takanori Matsui

Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors, serpins. It was first identified as a neuronal differentiating factor secreted by human retinal pigment epithelial cells, and then found to be the most potent inhibitor of pathological angiogenesis in mammalian eyes. Recently, PEDF has been shown not only to suppress oxidative stress and inflammatory reactions in vascular wall cells, T cells and macrophages, and adipocytes, but also to exert antithrombotic and anti-fibrotic properties, thereby protecting against the development and progression of various cardiometabolic diseases and related complications. Furthermore, accumulating evidence has suggested that circulating PEDF levels may be a biomarker of severity and prognosis of these devastating disorders. Number of subjects with visceral obesity and insulin resistance is increasing, and the metabolic syndrome and its related complications, such as diabetes, nonalcoholic fatty liver disease/non-alcoholic steatohepatits, and atherosclerotic cardiovascular disease are a growing health challenge. Therefore, in this study, we review the pathophysiological role of PEDF in obesity and metabolic disorders, cardiovascular disease, diabetic eye and kidney complications, liver diseases, and reproductive system disorders, and discuss the potential clinical utility of modulating the expression and actions of PEDF for preventing these cardiometabolic disorders. We also refer to the clinical value of PEDF as a biomarker in cardiometabolic complications.


2018 ◽  
Vol 15 (1) ◽  
pp. 44-48 ◽  
Author(s):  
Melanie Copenhaver ◽  
Chack-Yung Yu ◽  
Robert P. Hoffman

Introduction: Increased systemic inflammation plays a significant role in the development of adult cardiometabolic diseases such as insulin resistance, dyslipidemia, atherosclerosis, and hypertension. The complement system is a part of the innate immune system and plays a key role in the regulation of inflammation. Of particular importance is the activation of complement components C3 and C4. C3 is produced primarily by the liver but is also produced in adipocytes, macrophages and endothelial cells, all of which are present in adipose tissues. Dietary fat and chylomicrons stimulate C3 production. Adipocytes in addition to producing C3 also have receptors for activated C3 and other complement components and thus also respond to as well as produce a target for complement. C3adesArg, also known as acylation stimulation factor, increases adipocyte triglyceride synthesis and release. These physiological effects play a significant role in the development of metabolic syndrome. Epidemiologically, obese adults and non-obese adults with cardiometabolic disease who are not obese have been shown to have increased complement levels. C4 levels also correlate with body mass index. Genetically, specific C3 polymorphisms have been shown to predict future cardiovascular events and. D decreased C4 long gene copy number is associated with increased longevity. Conclusion: Future research is clearly needed to clarify the role of complement in the development of cardiovascular disease and mechanisms for its action. The complement system may provide a new area for intervention in the prevention of cardiometabolic diseases.


2021 ◽  
Vol 22 (8) ◽  
pp. 4137
Author(s):  
Jan Frohlich ◽  
George N. Chaldakov ◽  
Manlio Vinciguerra

Studies over the past 30 years have revealed that adipose tissue is the major endocrine and paracrine organ of the human body. Arguably, adiopobiology has taken its reasonable place in studying obesity and related cardiometabolic diseases (CMDs), including Alzheimer’s disease (AD), which is viewed herein as a neurometabolic disorder. The pathogenesis and therapy of these diseases are multiplex at basic, clinical and translational levels. Our present goal is to describe new developments in cardiometabolic and neurometabolic adipobiology. Accordingly, we focus on adipose- and/or skeletal muscle-derived signaling proteins (adipsin, adiponectin, nerve growth factor, brain-derived neuroptrophic factor, neurotrophin-3, irisin, sirtuins, Klotho, neprilysin, follistatin-like protein-1, meteorin-like (metrnl), as well as growth differentiation factor 11) as examples of metabotrophic factors (MTFs) implicated in the pathogenesis and therapy of obesity and related CMDs. We argue that these pathologies are MTF-deficient diseases. In 1993 the “vascular hypothesis of AD” was published and in the present review we propose the “vasculometabolic hypothesis of AD.” We discuss how MTFs could bridge CMDs and neurodegenerative diseases, such as AD. Greater insights on how to manage the MTF network would provide benefits to the quality of human life.


2021 ◽  
pp. 002203452199542
Author(s):  
B. Holtfreter ◽  
B. Stubbe ◽  
S. Gläser ◽  
J. Trabandt ◽  
H. Völzke ◽  
...  

Although a potential link between periodontitis and cardiorespiratory fitness might provide a reasonable explanation for effects of tooth-related alterations seen on cardiometabolic diseases, evidence is currently limited. Thus, we investigated the association between clinically assessed periodontitis and cardiopulmonary exercise testing (CPET). Data from 2 independent cross-sectional population-based studies (5-y follow-up of the Study of Health in Pomerania [SHIP-1; N = 1,639] and SHIP-Trend-0 [ N = 2,439]) were analyzed. Participants received a half-mouth periodontal examination, and teeth were counted. CPET was based on symptom limited-exercise tests on a bicycle ergometer. Associations of periodontitis parameters with CPET parameters were analyzed by confounder-adjusted multivariable linear regression. In the total sample, mean pocket probing depth (PPD), mean clinical attachment levels, and number of teeth were consistently associated with peak oxygen uptake (peakVO2) and exercise duration in both studies, even after restriction to cardiorespiratory healthy participants. Statistically significant associations with oxygen uptake at anaerobic threshold (VO2@AT), slope of the efficiency of ventilation in removing carbon dioxide, and peak oxygen pulse (VÉ/VCO2 slope) occurred. Further, interactions with age were identified, such that mainly older individuals with higher levels of periodontal disease severity were associated with lower peakVO2. Restricted to never smokers, associations with mean clinical attachment levels and the number of teeth mostly diminished, while associations of mean PPD with peakVO2, VO2@AT, VÉ/VCO2 slope, and exercise duration in SHIP-1 and SHIP-Trend-0 were confirmed. In SHIP-1, mean peakVO2 was 1,895 mL/min in participants with a mean PPD of 1.6 mm and 1,809 mL/min in participants with a mean PPD of 3.7 mm. To conclude, only mean PPD reflecting current disease severity was consistently linked to cardiorespiratory fitness in 2 cross-sectional samples of the general population. If confirmed in well-designed large-scale longitudinal studies, the association between periodontitis and cardiorespiratory fitness might provide a biologically plausible mechanism linking periodontitis with cardiometabolic diseases.


2021 ◽  
Author(s):  
Sardar Sindhu ◽  
Yat Hei Leung ◽  
Hossein Arefanian ◽  
S. R. Murthy Madiraju ◽  
Fahd Al‐Mulla ◽  
...  

2021 ◽  
Author(s):  
Curtis Tilves ◽  
Joseph M. Zmuda ◽  
Allison L Kuipers ◽  
Sangeeta Nair ◽  
J Jeffrey Carr ◽  
...  

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 123
Author(s):  
Álvaro Sosa Liprandi ◽  
Ezequiel José Zaidel ◽  
Ricardo Lopez Santi ◽  
John Jairo Araujo ◽  
Manuel Alfonso Baños González ◽  
...  

Background: Influenza vaccination (IV) and Pneumococcus vaccination (PV) are recommended for patients with cardiometabolic diseases. This study aimed to evaluate the immunization rate of ambulatory cardiometabolic patients during the COVID-19 pandemic in the Americas. Methods: Electronic surveys were collected from 13 Spanish speaking countries between 15 June and 15 July 2020. Results: 4216 patients were analyzed. Mean age 60 (±15) years and 49% females. Global IV rate was 46.5% and PV 24.6%. Vaccinated patients were older (IV = 63 vs. 58 years; PV = 68 vs. 59, p < 0.01) but without gender difference. Vaccination rates were greater in higher-risk groups (65+, diabetics, heart failure), but not in coronary artery disease patients. In the Southern cone, the rate of IV and PV was approximately double that in the tropical regions of the Americas. In a multivariate model, geographic zone (IV = OR 2.02, PV = OR 2.42, p < 0.001), age (IV = OR 1.023, PV = OR 1.035, p < 0.001), and incomes (IV = OR 1.28, PV = OR 1.58, p < 0.001) were predictors for vaccination. Conclusions: During the COVID-19 pandemic, ambulatory patients with cardiometabolic diseases from the Americas with no evidence of COVID-19 infection had lower-than-expected rates of IV and PV. Geographic, social, and cultural differences were found, and they should be explored in depth.


2021 ◽  
pp. svn-2020-000693
Author(s):  
Yanan Qiao ◽  
Siyuan Liu ◽  
Guochen Li ◽  
Yanqiang Lu ◽  
Ying Wu ◽  
...  

Background and purposeThe role of depression in the development and outcome of cardiometabolic diseases remains to be clarified. We aimed to examine the extent to which depressive symptoms affect the transitions from healthy to diabetes, stroke, heart disease and subsequent all-cause mortality in a middle-aged and elderly European population.MethodsA total of 78 212 individuals aged ≥50 years from the Survey of Health Ageing and Retirement in Europe were included. Participants with any baseline cardiometabolic diseases including diabetes, stroke and heart disease were excluded. Depressive symptoms were measured by the Euro-Depression scale at baseline. Participants were followed up to determine the occurrence of cardiometabolic diseases and all-cause mortality. We used multistate models to estimate the transition-specific HRs and 95% CIs after adjustment of confounders.ResultsDuring 500 711 person-years of follow-up, 4742 participants developed diabetes, 2173 had stroke, 5487 developed heart disease and 7182 died. Depressive symptoms were significantly associated with transitions from healthy to diabetes (HR: 1.12, 95% CI: 1.05 to 1.20), stroke (HR: 1.31, 95% CI: 1.18 to 1.44), heart disease (HR: 1.26, 95% CI: 1.18 to 1.34) and all-cause mortality (HR: 1.41, 95% CI: 1.34 to 1.49). After cardiometabolic diseases, depressive symptoms were associated with the increased risk of all-cause mortality in patients with diabetes (HR: 1.54, 95% CI: 1.25 to 1.89), patients who had stroke (HR: 1.29, 95% CI: 1.03 to 1.61) and patients with heart disease (HR: 1.21, 95% CI: 1.02 to 1.44).ConclusionsDepressive symptoms increase the risk of diabetes, stroke and heart disease, and affect the risk of mortality after the onset of these cardiometabolic conditions. Screening and treatment of depressive symptoms may have profound implications for the prevention and prognosis of cardiometabolic diseases.


2019 ◽  
Vol 8 (2) ◽  
pp. 10 ◽  
Author(s):  
Gonçalves-Dias ◽  
Morello ◽  
Semedo ◽  
Correia ◽  
Coelho ◽  
...  

The mercapturate pathway is a unique metabolic circuitry that detoxifies electrophiles upon adducts formation with glutathione. Since its discovery over a century ago, most of the knowledge on the mercapturate pathway has been provided from biomonitoring studies on environmental exposure to toxicants. However, the mercapturate pathway-related metabolites that is formed in humans—the mercapturomic profile—in health and disease is yet to be established. In this paper, we put forward the hypothesis that these metabolites are key pathophysiologic factors behind the onset and development of non-communicable chronic inflammatory diseases. This review goes from the evidence in the formation of endogenous metabolites undergoing the mercapturate pathway to the methodologies for their assessment and their association with cancer and respiratory, neurologic and cardiometabolic diseases.


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