DUSP1 Is a Potential Marker of Chronic Inflammation in Arabs with Cardiovascular Diseases

Background. Cardiovascular disease (CVD) risks persist in patients despite the use of conventional treatments. This might be due to chronic inflammation as reflected in epidemiological studies associating circulating low-grade inflammatory markers with CVD recurrent events. Here, we explored this potential link by assessing plasma dual-specificity phosphatase 1 (DUSP1) levels and comparing them to high-sensitivity CRP (hsCRP) and oxidized low-density lipoprotein (oxLDL) levels and their associations to conventional CVD risk factors in confirmed CVD patients. Methods. Human adults with reported CVD (n=207) and controls (n=70) living in Kuwait were used in this study. Anthropometric and classical biochemical parameters were determined. Plasma levels of DUSP1, oxLDL, and hsCRP were measured using human enzyme-linked immunosorbent assay kits. Results. DUSP1 and hsCRP plasma levels and their least square means were higher in CVD cases, while oxLDL plasma levels were lower (p<0.05). Multivariate logistic regression analysis showed that DUSP1 and hsCRP are independently associated with CVD in the studied population, as reflected by 2-fold and 1.5-fold increased risks with increased levels of DUSP1 and hsCRP, respectively. In our study, DUSP1 levels were found to be associated with CVD despite statin treatment and diabetes status (p<0.05), whereas hsCRP mainly correlated with obesity markers. Conclusions. Circulating DUSP1 might be a predictor of chronic subclinical inflammation and residual risk in CVD patients, whereas our data suggest that the association between hsCRP and CVD is largely accounted for adiposity risk factors.

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Empagliflozin reverses obesity and insulin resistance through fat browning and alternative macrophage activation in mice fed a high-fat diet

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000783 ◽

2019 ◽

Vol 7 (1) ◽

pp. e000783 ◽

Cited By ~ 7

Author(s):

Liang Xu ◽

Naoto Nagata ◽

Guanliang Chen ◽

Mayumi Nagashimada ◽

Fen Zhuge ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Energy Expenditure ◽

Chronic Inflammation ◽

Plasma Levels ◽

High Fat Diet ◽

Macrophage Activation ◽

Low Grade ◽

Obese Mice ◽

High Fat

ObjectiveWe reported previously that empagliflozin—a sodium-glucose cotransporter (SGLT) 2 inhibitor—exhibited preventive effects against obesity. However, it was difficult to extrapolate these results to human subjects. Here, we performed a therapeutic study, which is more relevant to clinical situations in humans, to investigate antiobesity effects of empagliflozin and illustrate the mechanism underlying empagliflozin-mediated enhanced fat browning in obese mice.Research design and methodsAfter 8 weeks on a high-fat diet (HFD), C57BL/6J mice exhibited obesity, accompanied by insulin resistance and low-grade chronic inflammation. Cohorts of obese mice were continued on the HFD for an additional 8-week treatment period with or without empagliflozin.ResultsTreatment with empagliflozin for 8 weeks markedly increased glucose excretion in urine, and suppressed HFD-induced weight gain, insulin resistance and hepatic steatosis. Notably, empagliflozin enhanced oxygen consumption and carbon dioxide production, leading to increased energy expenditure. Consistently, the level of uncoupling protein 1 expression was increased in both brown and white (WAT) adipose tissues of empagliflozin-treated mice. Furthermore, empagliflozin decreased plasma levels of interleukin (IL)-6 and monocyte chemoattractant protein-1, but increased plasma levels of IL-33 and adiponectin in obese mice. Finally, we found that empagliflozin reduced M1-polarized macrophage accumulation, while inducing the anti-inflammatory M2 phenotype of macrophages in the WAT and liver, thereby attenuating obesity-related chronic inflammation.ConclusionsTreatment with empagliflozin attenuated weight gain by increasing energy expenditure and adipose tissue browning, and alleviated obesity-associated inflammation and insulin resistance by alternative macrophage activation in the WAT and liver of obese mice.

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Association of Omentin-1 and Central Obesity with Coronary Heart Disease

Pakistan Journal of Medicine and Dentistry ◽

10.36283/pjmd9-4/002 ◽

2020 ◽

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Heart Disease ◽

Heart Disease ◽

Coronary Artery ◽

Waist Circumference ◽

Central Obesity ◽

Multivariate Logistic Regression Analysis ◽

Enzyme Linked Immunosorbent Assay ◽

Artery Disease

Background: Omentin-1 is a novel adipocytokine expressed from visceral adipose tissues and is closely associated with obesity, inﬂammation and coronary artery disease. Central or abdominal obesity has a dynamic role in the development of coronary heart disease by enviably effecting conventional risk factors. Waist circumference is a sensitive, reliable and speciﬁc anthropometrical indicator of central obesity. Thus, the present study aimed to evaluate the correlation between central obesity measured by waist circumference and plasma omentin-1 in patients with coronary heart disease. Methods: The study was performed in cardiac unit of Civil Hospital Karachi and Karachi Institute of Heart Diseases (KIHD), Pakistan from January 2016-August 2016. A total of 250 patients (92 females, 158 males) with coronary artery disease were evaluated. Waist circumference was measured at the level of umbilicus. Determination of Omentin-1 was done by an enzyme-linked immunosorbent assay (ELISA). Data was evaluated by SPSS and one way ANOVA was performed to determine the baseline characteristics of study population. Pearson’s correlation was used for association between waist circumference and plasma omentin-1. Results: There was a negative association between waist circumference and plasma omentin-1 (R = -0.68, p < 0.01) in males and (R= – 0.50, p < 0.01) in female patients of coronary heart disease. Waist circumference was found an independent determinant of circulating omentin-1 while performing multivariate logistic regression analysis, after adjusting cardio-metabolic risk factors like age, body mass index, lipid proﬁle, blood sugar levels and smoking. Conclusion: There was a negative correlation of plasma omentin-1 and central obesity in coronary heart disease. Keywords: Central Obesity; Coronary Heart Disease; Omentin-1; Waist Circumference.

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Seroepidemiology of Toxoplasma gondii infection in patients with liver disease in eastern China

Epidemiology and Infection ◽

10.1017/s0950268817001327 ◽

2017 ◽

Vol 145 (11) ◽

pp. 2296-2302 ◽

Cited By ~ 18

Author(s):

A. L. TIAN ◽

G. X. LI ◽

H. M. ELSHEIKHA ◽

D. S. GARDNER ◽

X. Y. ZHANG ◽

...

Keyword(s):

Risk Factors ◽

Liver Disease ◽

Toxoplasma Gondii ◽

Eastern China ◽

Multivariate Logistic Regression Analysis ◽

Protozoan Parasite ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Igm Antibodies ◽

Toxoplasma Gondii Infection

SUMMARYThe role of the protozoan parasite Toxoplasma gondii in the pathogenesis of liver disease has recently gained much interest. The aim of this study was to determine the prevalence and risk factors associated with T. gondii infection in patients with liver disease from three cities in Shandong and Henan provinces, China. A case–control study was conducted from December 2014 to November 2015 and included 1142 patients with liver disease and 1142 healthy controls. Serum samples were collected from all individuals and were examined with enzyme-linked immunosorbent assay for the presence of anti-T. gondii IgG and IgM antibodies. Information on the demographics, clinical, and lifestyle characteristics of the participants was collected from the medical records and by the use of a questionnaire. The prevalence of anti-T. gondii IgG was 19·7% in patients with liver disease compared with 12·17% in the controls. Only 13 patients had anti-T. gondii IgM antibodies compared with 12 control individuals (1·14% vs. 1·05%, respectively). The highest seroprevalence was detected in patients with liver cancer (22·13%), followed by hepatitis patients (20·86%), liver cirrhosis patients (20·42%), and steatosis patients (20%). Multivariate logistic regression analysis indicated that consumption of raw meat (odds ratio (OR) = 1·32; 95% confidence interval (CI) 1·01–1·71; P = 0·03) and source of drinking water from wells (OR = 1·56; 95% CI 1·08–2·27; P = 0·01) were independent risk factors for T. gondii infection in liver disease patients. These findings indicate that T. gondii infection is more likely to be present in patients with liver disease. Therefore, efforts should be directed toward health education of populations at high risk of T. gondii infection and measures should be taken to protect vulnerable patients with liver disease.

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Inflammatory Cytokine-Producing Cells and Inflammation Markers in the Synovium of Osteoarthritis Patients Evidenced in Human Herpesvirus 7 Infection

International Journal of Molecular Sciences ◽

10.3390/ijms21176004 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6004

Author(s):

Valerija Groma ◽

Mihails Tarasovs ◽

Sandra Skuja ◽

Sofija Semenistaja ◽

Zaiga Nora-Krukle ◽

...

Keyword(s):

Endothelial Cells ◽

Plasma Levels ◽

Synovial Membrane ◽

Vascular Endothelial Cells ◽

Human Herpesvirus ◽

Joint Disease ◽

Enzyme Linked Immunosorbent Assay ◽

Low Grade ◽

Vascular Endothelial ◽

Tissue Samples

A direct association between joint inflammation and the progression of osteoarthritis (OA) has been proposed, and synovitis is considered a powerful driver of the disease. Among infections implicated in the development of joint disease, human herpesvirus 7 (HHV-7) infection remains poorly characterized. Therefore, we assessed synovitis in OA patients; determined the occurrence and distribution of the HHV-7 antigen within the synovial membrane of OA-affected subjects; and correlated plasma levels of the pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin-6 (IL-6), and TNF expressed locally within lesioned synovial tissues with HHV-7 observations, suggesting differences in persistent latent and active infection. Synovial HHV-7, CD4, CD68, and TNF antigens were detected immunohistochemically. The plasma levels of TNF and IL-6 were measured by an enzyme-linked immunosorbent assay. Our findings confirm the presence of persistent HHV-7 infection in 81.5% and reactivation in 20.5% of patients. In 35.2% of patients, virus-specific DNA was extracted from synovial membrane tissue samples. We evidenced the absence of histopathologically detectable synovitis and low-grade changes in the majority of OA patients enrolled in the study, in both HHV-7 PCR+ and HHV-7 PCR‒ groups. The number of synovial CD4-positive cells in the HHV-7 polymerase chain reaction (PCR)+ group was significantly higher than that in the HHV-7 PCR‒ group. CD4- and CD68-positive cells were differently distributed in both HHV-7 PCR+ and HHV-7 PCR‒ groups, as well as in latent and active HHV-7 infection. The number of TNF+ and HHV-7+ lymphocytes, as well as HHV-7+ vascular endothelial cells, was strongly correlated. Vascular endothelial cells, especially in the case of infection reactivation, appeared vulnerable. The balance between virus latency and reactivation is a long-term relationship between the host and infectious agent, and the immune system appears to be involved in displaying overreaction when a shift in the established equilibrium develops.

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Toxoplasma gondii infection among pregnant women in Yemen: Factors associated with high seroprevalence

The Journal of Infection in Developing Countries ◽

10.3855/jidc.6638 ◽

2016 ◽

Vol 10 (06) ◽

pp. 667-672 ◽

Cited By ~ 5

Author(s):

Samira M. Al-Eryani ◽

Abdulsalam M Al-Mekhlafi ◽

Latifa A Al-Shibani ◽

Mohammed M. K. Mahdy ◽

Ahmed A Azazy

Keyword(s):

Risk Factors ◽

Toxoplasma Gondii ◽

Pregnant Women ◽

Demographic Data ◽

Multivariate Logistic Regression Analysis ◽

Public Health Problem ◽

Capital City ◽

Enzyme Linked Immunosorbent Assay ◽

High Seroprevalence ◽

Important Public Health Problem

Introduction: Although toxoplasmosis is an important public health problem, there is scarcity of data on the disease available from Yemen. A cross-sectional survey was conducted in health facilities to determine seroprevalence of Toxoplasma gondii and associated risk factors among pregnant women in Sana’a, the capital city of Yemen. Methodology: A total of 593 pregnant women were included and examined for anti-T. gondii antibodies (Ab) using enzyme-linked immunosorbent assay. Bio and socio-demographic data were collected by pre-tested structured questionnaires through face-to-face interviews. Results: The overall seroprevalence of T. gondii was 45.4% (95% confidence interval: 41%–49%). The prevalence of anti-T. gondii IgG and IgM was 43.7 (95% CI: 40–%48%) and 9.1% (95% CI: 7%–12%), respectively. About 7.4 (95% CI: 6%–10%) of pregnant women were seropositive for both IgG and IgM Abs. Multivariate logistic regression analysis identified the following risk factors for toxplasmosis (IgG and/or IgM): age ≥ 25 years (adjusted OR: 2.02, 95% CI: 1.44–2.84, p < 0.001), rearing cats in the house (OR: 1.75, 95% CI: 1.20–2.55, p = 0.004), and contact with soil (OR: 1.90, 95% CI: 1.32–2.75, p = 0.001). Conclusions: The study reported high seroprevalence among pregnant women in Sana’a, Yemen, with a high proportion of pregnant women having a possibility of acute toxoplasmosis. This highlights the need for including routine screening for T. gondii in pregnant women in the country’s antenatal clinics. In addition, health education on the mode of transmission of toxoplasmosis should be provided for pregnant women in Yemen.

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Chronic Inflammation in Peritoneal Dialysis: The Search for the Holy Grail?

Peritoneal Dialysis International ◽

10.1177/089686080402400407 ◽

2004 ◽

Vol 24 (4) ◽

pp. 327-339 ◽

Cited By ~ 55

Author(s):

Roberto Pecoits–Filho ◽

Peter Stenvinkel ◽

Angela Yee-Moon Wang ◽

Olof Heimbürger ◽

Bengt Lindholm

Keyword(s):

Risk Factors ◽

Peritoneal Dialysis ◽

General Population ◽

Chronic Inflammation ◽

Systemic Inflammation ◽

Stable Condition ◽

Morbidity And Mortality ◽

Low Grade ◽

Dialysis Therapy ◽

Low Grade Inflammation

Mortality and morbidity in chronic kidney disease (CKD) patients are unacceptably high. The annual mortality rate due to cardiovascular disease (CVD) is approximately 9%, which, for the middle-aged person, is at least 10- to 20-fold higher than for the general population. Classic risk factors for CVD are highly prevalent in CKD patients, but they cannot fully account for the excessive rate of CVD in this population. Instead, it has become increasingly clear that nontraditional risk factors, such as systemic inflammation, may play a key role in the development of atherosclerosis. It is well established that inflammatory markers are very powerful predictors of high CVD morbidity and mortality not only in the general population, but particularly in CKD patients. Signs of a sustained low-grade inflammation, such as increased levels of C-reactive protein (CRP), are present in the majority of stage 5 CKD patients, even in patients in clinically stable condition, and they are also commonly observed after the initiation of dialysis therapy. Dialysis therapy — hemodialysis as well as peritoneal dialysis (PD) — may itself contribute to systemic inflammation. Local intraperitoneal inflammation can also occur in patients treated with PD. These local effects may result in a low-grade inflammation, caused by the bioincompatibility of conventional glucose-based dialysis fluids, to intense inflammation associated with peritonitis. Given these circumstances, it is reasonable to hypothesize that strategies aiming to reduce inflammation are potentially important and novel, and could serve to reduce CVD, thereby lowering morbidity and mortality in patients with CKD. In this review we provide information supporting the hypothesis that systemic inflammation is tightly linked to the most common complications of CKD patients, in particular those on PD, and that local inflammation in PD may contribute to various related complications. The aims of this review are to discuss the reasons that make inflammation an attractive target for intervention in CKD, the particular aspects of the inflammation–CVD axis during PD treatment that are likely involved, and possible means for the detection and management of chronic inflammation in PD patients.

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The Effect of Low-Grade Chronic Inflammation on the Pathogenesis of Metabolic Syndrome

10.14293/s2199-1006.1.sor-.ppbgbyn.v1 ◽

2020 ◽

Author(s):

MARINA GERGES

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Chronic Inflammation ◽

Tissue Injury ◽

Strong Association ◽

High Sensitivity ◽

Low Grade ◽

Obese People ◽

Alcoholic Fatty Liver ◽

Chronic Inflammatory Condition

It is well accepted that metabolic syndrome (MS) increases the risk for the development of cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), stroke and cancer [1] . Recently, the chronic inflammatory condition that often accompanies the MS has been implicated as a major factor both in the installation of the MS itself and its associated pathophysiological consequences [2] . However, the inflammatory state that accompanies the MS does not completely fit into the classical definition of acute or chronic inflammation, as it is not accompanied by infection; there is no massive tissue injury and the dimension of the inflammatory activation is also not large. So, it is often called low-grade chronic inflammation or meta-inflammation , meaning metabolically-triggered inflammation [3] . Several studies support the concept that a proinflammatory state is a component of the MS because of the strong association of elevated C-reactive protein (CRP) with MS-risk factors and high CRP levels impart risk for major coronary events beyond that imparted by the other metabolic risk factors. High-sensitivity CRP (hs-CRP) has been developed and used as a marker to predict coronary vascular diseases in the MS and it was recently used as a predictor for non-alcoholic fatty liver disease (NAFLD) in correlation with serum markers that indicated lipid and glucose metabolism. However, the reasons for a link between inflammation and MS are not fully understood. One explanation may be that adipose tissue in obese people with MS releases increased amounts of cytokines into the circulation which in turn accounts for a greater production of CRP by the liver. Another possibility is that insulin resistance (IRalone is responsible for higher production of cytokines. Regardless of the mechanism, the finding that patients with MS exhibit characteristics of a proinflammatory state provide a new and exciting connection between inflammation and metabolic processes.

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Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

Clinical Science ◽

10.1042/cs20190999 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2283-2299

Author(s):

Apabrita Ayan Das ◽

Devasmita Chakravarty ◽

Debmalya Bhunia ◽

Surajit Ghosh ◽

Prakash C. Mandal ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Chronic Inflammation ◽

Ex Vivo ◽

Human Subjects ◽

Critical Role ◽

Atherosclerotic Cardiovascular Disease ◽

Tnf Α ◽

Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

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