scholarly journals Neutral sphingomyelinase‐2 and cardiometabolic diseases

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

Pigment Epithelium-Derived Factor: A Novel Therapeutic Target for Cardiometabolic Diseases and Related Complications

2018 ◽  
Vol 25 (13) ◽  
pp. 1480-1500 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Takanori Matsui
Keyword(s):  
Cardiovascular Disease ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Visceral Obesity ◽  
Retinal Pigment Epithelial Cells ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cardiometabolic Diseases ◽  
The Metabolic Syndrome ◽  
Pigment Epithelium Derived Factor ◽  
Cardiometabolic Disorders

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.

Complement Components, C3 and C4, and the Metabolic Syndrome

2018 ◽  
Vol 15 (1) ◽  
pp. 44-48 ◽  
Author(s):  
Melanie Copenhaver ◽  
Chack-Yung Yu ◽  
Robert P. Hoffman
Keyword(s):  
Metabolic Syndrome ◽  
Significant Role ◽  
Complement System ◽  
Gene Copy ◽  
Future Research ◽  
Obese Adults ◽  
Complement Components ◽  
Cardiometabolic Diseases ◽  
The Metabolic Syndrome ◽  
The Complement System

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.

scholarly journals Regulatory T cells reduce endothelial neutral sphingomyelinase 2 to prevent T cell migration into tumors

2021 ◽  
Author(s):  
Paulina Akeus ◽  
Louis Szeponik ◽  
Veronica Langenes ◽  
Viktoria Karlsson ◽  
Patrik Sundström ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Migration ◽  
T Cell ◽  
Regulatory T Cells ◽  
Neutral Sphingomyelinase ◽  
T Cell Migration

scholarly journals Physiological functions and therapeutic applications of neutral sphingomyelinase and acid sphingomyelinase

2021 ◽  
Vol 139 ◽  
pp. 111610
Author(s):  
Hongjiao Xiang ◽  
Shengjie Jin ◽  
Fenglang Tan ◽  
Yifan Xu ◽  
Yifei Lu ◽  
...  
Keyword(s):  
Acid Sphingomyelinase ◽  
Physiological Functions ◽  
Therapeutic Applications ◽  
Neutral Sphingomyelinase

scholarly journals Cardio- and Neurometabolic Adipobiology: Consequences and Implications for Therapy

2021 ◽  
Vol 22 (8) ◽  
pp. 4137
Author(s):  
Jan Frohlich ◽  
George N. Chaldakov ◽  
Manlio Vinciguerra
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Nerve Growth Factor ◽  
Human Life ◽  
Signaling Proteins ◽  
New Developments ◽  
Cardiometabolic Diseases ◽  
The Past ◽  
Neurotrophin 3

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.

Periodontitis Is Related to Exercise Capacity: Two Cross-sectional Studies

2021 ◽  
pp. 002203452199542
Author(s):  
B. Holtfreter ◽  
B. Stubbe ◽  
S. Gläser ◽  
J. Trabandt ◽  
H. Völzke ◽  
...  
Keyword(s):  
Oxygen Uptake ◽  
Disease Severity ◽  
Cardiorespiratory Fitness ◽  
Large Scale ◽  
Cardiopulmonary Exercise Testing ◽  
Exercise Duration ◽  
Cross Sectional ◽  
Sample Mean ◽  
Cardiometabolic Diseases ◽  
Number Of Teeth

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.

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