scholarly journals CD147 Levels in Blood and Adipose Tissues Correlate with Vascular Dysfunction in Obese Diabetic Adults

2021 ◽  
Vol 9 (1) ◽  
pp. 7
Author(s):  
Mohamed M. Ali ◽  
Imaduddin Mirza ◽  
Dina Naquiallah ◽  
Chandra Hassan ◽  
Mario Masrur ◽  
...  
Keyword(s):  
Fat Mass ◽  
Vascular Function ◽  
Cardiometabolic Risk ◽  
Pulse Wave ◽  
Vascular Dysfunction ◽  
Glucose Levels ◽  
Glycation End Products ◽  
Obese Subjects ◽  
Visceral Adipose ◽  
Circulating Levels

CD147 is a glycoprotein that stimulates the production of matrix metalloproteinases (MMPs), known contributors to cardiovascular risk. The activity of CD147 protein depends on its glycosylation. However, it is unclear whether CD147 protein expression or glycosylation are influenced by the diabetic milieu characterized by hyperglycemia and abundant glycation-end-products (AGEs). We examined the circulating and visceral adipose tissue (VAT) levels of CD147 and their correlation with vascular function in obese, obese diabetic, and non-obese controls (n = 40, each). The circulating levels of CD147 and the glycosylated CD147 protein in VAT were considerably higher in obese, particularly obese diabetic subjects compared to controls. Obese diabetics had the lowest brachial and arteriolar vasoreactivity and the highest carotid pulse-wave velocity (PWV, a measure of arterial stiffness) among the three groups. CD147 correlated positively with body mass index (BMI), total and visceral fat mass, PWV, and plasma levels of glucose, insulin, MMPs, and AGEs and negatively with brachial artery and VAT-arteriolar vasoreactivity and nitric oxide production. Multivariate regression revealed that BMI, body fat mass, insulin, and glucose levels significantly predicted CD147. Our data suggest that higher levels of CD147 in obese subjects, particularly those with diabetes, are linked to vascular dysfunction and several cardiometabolic risk factors.

Abstract P006: Liraglutide Attenuates Cardiac Fibrosis and Vascular Dysfunction in a Non-diabetic Angiotensin II-infusion Model via Anti-inflammatory and Anti-oxidant Mechanisms

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Huey Wen Lee ◽  
Melita Brdar ◽  
Robert Widdop ◽  
Anthony Dear ◽  
Tracey Gaspari
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Cardiac Fibrosis ◽  
Vascular Dysfunction ◽  
Cardiomyocyte Hypertrophy ◽  
High Dose ◽  
Protective Effects ◽  
Ang Ii ◽  
Treatment Protocols ◽  
Glucose Levels

Glucagon-like peptide-1 (GLP-1) based therapies are used to treat type II diabetes via increasing insulin secretion and inhibiting glucagon production. Recent evidence suggests that activating the GLP-1 receptor may also mediate direct vaso-protective effects. Therefore the objective of the study was to determine whether GLP-1R stimulation conferred cardio- and vaso-protection in a non-diabetic setting using the angiotensin (Ang) II infusion model of hypertension and cardiovascular dysfunction. Male C57Bl/6J mice (4-6 months) were assigned to one of the following 4 week treatment protocols: 1) vehicle (saline), 2) Ang II (800ng/kg/day), 3) Ang II + liraglutide (30μg/kg/day), 4) Ang II + liraglutide (300μg/kg/day). All treatments were administered via osmotic mini-pumps (s.c). After 4 weeks the effect of liraglutide treatment on blood pressure, vascular function and cardiac remodelling was examined. Liraglutide (both doses) attenuated Ang II-induced increase in systolic blood pressure (Ang II: 175.3 ± 8.6mmHg vs Ang II+Lirag (30) 150.2 ± 6.4 mmHg or Ang II+Lirag (300): 145.4 ± 6.9 mmHg) without affecting blood glucose levels. Liraglutide (both doses) completely prevented Ang II-induced endothelial dysfunction (% maximum relaxation: Ang II=50.7 ± 7.8%; Ang II+Lirag (30)=82.7 ± 5.8; Ang II+Lirag (300)=81.5 ± 6.1%). In the heart, liraglutide prevented Ang II-induced cardiomyocyte hypertrophy (n=7-10; p<0.05) and reduced collagen deposition (% collagen expression: Ang II=4.4 ± 0.5 vs Ang II+Lirag(300)=2.9 ± 0.3; n=7-9; p<0.01). This anti-fibrotic effect was attributed to reduced fibroblast/myofibroblast expression as well as decreased inflammation with reduced NFκB and MCP-1 expression and decreased oxidative stress with a significant reduction in superoxide production using high dose of liraglutide. Overall, stimulation of GLP-1R in a non-diabetic setting protected against Ang II-mediated cardiac hypertrophy, cardiac fibrosis and vascular dysfunction, indicating potential for use of GLP-1 based therapies in treatment of cardiovascular disease independent of diabetes.

scholarly journals Biochemistry of hyperglycemia induced vascular dysfunction

2013 ◽  
Vol 20 (4) ◽  
pp. 419-425 ◽  
Author(s):  
Cristina Muntean ◽  
Adina Mitrea ◽  
Simona Georgiana Popa ◽  
Valerica Tudorică ◽  
Maria Moţa
Keyword(s):  
Vascular Dysfunction ◽  
Polyol Pathway ◽  
Pentose Phosphate ◽  
Glut 1 ◽  
Glucose Levels ◽  
Kinase C ◽  
Hexosamine Pathway ◽  
Glycation End Products ◽  
End Products ◽  
Intracellular Glucose

Abstract Glucose enters the endothelium via a non-insulin sensitive GLUT-1 facilitated transporter that transports glucose continuously. Extracellular hyperglycemia is positively correlated with intracellular glucose. As the glucose levels increase, several changes in the glycolytic pathway, tricarboxilic acid cycle and the pentose phosphate pathway occur, all of them leading to an increase of oxygen reactive species (ROS). ROS are capable not only of directly impairing endothelial cells, but also indirectly by activating poly(ADPribose) polymerase, which inhibits glyceraldehyde 3-phosphate dehydrogenase. Further increase in glycloytic intermediates is followed by activation or overexpression of the main pathological pathways of hyperglycemia induced vascular damage: upregulation of glycation end-products, activation of protein kinase C, increased hexosamine pathway, and increased flux through polyol pathway, finally leading to the progressive narrowing and occlusion of the vessels.

scholarly journals Effects of Exenatide on both fat mass loss and cardiometabolic risk in obese subjects with type 2 diabetes mellitus

2017 ◽  
Vol 14 (7) ◽  
Author(s):  
Carmela Colica ◽  
Sara Parrettini ◽  
Giuseppe Merra ◽  
Lorenzo Romano ◽  
Laura Di Renzo ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mass Loss ◽  
Fat Mass ◽  
Cardiometabolic Risk ◽  
Obese Subjects ◽  
Fat Mass Loss

scholarly journals The crosstalk between insulin resistance, systemic inflammation, redox imbalance and the thyroid in subjects with obesity

2021 ◽  
Vol 8 (1) ◽  
pp. 139-148
Author(s):  
Nicoleta Răcătăianu ◽  
Nicoleta Leach ◽  
Sorana Bolboacă ◽  
Maria Soran ◽  
Mirela Flonta ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Systemic Inflammation ◽  
Cell Damage ◽  
Positive Association ◽  
Produce Cell ◽  
Monocyte Chemoattractant Protein 1 ◽  
Redox Imbalance ◽  
Obese Subjects ◽  
Visceral Adipose ◽  
Circulating Levels

We aimed at assessing the interaction between visceral adipose tissue (VAT), insulin resistance (IR), circulating levels of monocyte chemoattractant protein-1 (MCP-1) and malondialdehyde (MDA) and the thyroid parameters in obese subjects. Methods. Obese subjects without thyroid pathologies or diseases associated with systemic inflammation and OS were recruited. Insulinemia, visceral fat thickness, metabolic and thyroid parameters were assayed. Circulating levels of MCP-1 and MDA were used to quantify inflammation and OS. Results. A number of 160 obese subjects were included. The MCP-1 level increased with the degree of obesity and HOMA-IR. MCP 1 was positively associated with antithyroperoxidase antibody (TPOab) levels and the frequency of Hashimoto’s thyroiditis (HT). The MDA level was positively correlated with the degree of obesity, aspartate aminotransferase and MCP-1. MDA was an independent predictor for the occurrence of hypothyroidism. IR patients showed higher fT3 levels and a positive association between insulin and TPOab levels. Conclusions. Systemic inflammation increased with VAT, IR and OS and was correlated with the frequency and the severity of HT, suggesting that, in obesity, MCP-1 could be part of the etiopathogenesis of autoimmune thyroiditis. MDA was an independent risk factor for hypothyroidism; therefore, redox imbalance associated with obesity can produce cell damage and thyroid dysfunction. FT3 is increased in IR patients, thus being a marker for the severity of metabolic impairment.

Perivascular adipose tissue, inflammation and insulin resistance: link to vascular dysfunction and cardiovascular disease

2015 ◽  
Vol 22 (1) ◽  
Author(s):  
Guido Lastra ◽  
Camila Manrique
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Small Diameter ◽  
Perivascular Adipose Tissue ◽  
Anti Inflammatory ◽  
Visceral Adipose

AbstractObesity is a leading risk factor for the development of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD), however the underlying mechanisms still remain to be fully uncovered. It is now well accepted that dysfunctional adipose tissue in conditions of obesity is a critical source of inflammation that impacts the cardiovascular system and contributes to CVD. Although traditionally visceral adipose tissue has been linked to increased CVD risk, there is mounting interest in the role that fat accumulation around the vasculature plays in the pathogenesis of vascular dysfunction. Perivascular adipose tissue (PVAT) is in intimate contact with large, medium and small diameter arterial beds in several tissues, and has been shown to control vascular function as well as remodeling. PVAT does not merely mirror visceral adipose tissue changes seen in obesity, but has unique features that impact vascular biology. In lean individuals PVAT exerts vasodilatory and anti-inflammatory functions, however obesity results in PVAT inflammation, characterized by imbalance between pro- and anti-inflammatory cells as wells as adipokines. PVAT inflammation promotes insulin resistance in the vasculature, thus resulting in impaired insulin-mediated vasodilatory responses and vascular remodeling. In this review we address current knowledge about the mechanisms that link PVAT inflammation to insulin resistance and vascular dysfunction. Indeed, PVAT emerges as a novel type of adipose tissue that participates in the pathogenesis of CVD, independently to a large extent to visceral adipose tissue.

Visceral adipose tissue and body fat mass: Predictive values for and role of gender in cardiometabolic risk among Turks

Nutrition ◽  
2010 ◽  
Vol 26 (4) ◽  
pp. 382-389 ◽  
Author(s):  
Altan Onat ◽  
Murat Uğur ◽  
Günay Can ◽  
Hüsniye Yüksel ◽  
Gülay Hergenç
Keyword(s):  
Adipose Tissue ◽  
Body Fat ◽  
Fat Mass ◽  
Visceral Adipose Tissue ◽  
Cardiometabolic Risk ◽  
Body Fat Mass ◽  
Predictive Values ◽  
Visceral Adipose

Abstract P213: Western Diet May Modulate Kidney Injury and Albuminuria Differentially in Female Mice Deficient in Mr in the Endothelium versus the Smooth Muscle

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Ravi Nistala ◽  
Ruth Simpson ◽  
Javad Habibi ◽  
Annayya Aroor ◽  
Mona Garro ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulse Wave Velocity ◽  
Wave Velocity ◽  
Vascular Function ◽  
Pulse Wave ◽  
Vascular Dysfunction ◽  
Kidney Injury ◽  
Protective Role ◽  
Western Diet ◽  
Western Blots

Activation of the mineralocorticoid receptor (MR) has been implicated in kidney injury and precipitation of proteinuria. In this regard, diet induced obesity (DIO), a condition of MR activation is characterized by increase in kidney injury and proteinuria. DIO and other conditions of MR activation also manifest vascular dysfunction that may play a role in kidney injury and proteinuria. Vascular dysfunction may be endothelial or smooth muscle mediated. Moreover, MR signaling in the endothelium versus smooth muscle may be important in vascular function. Data from the Jaffe lab and our preliminary data show that deficiency of smooth muscle and endothelial MR plays a protective role from vascular dysfunction such as increased pulse wave velocity and stiffness. However, the role of endothelial specific versus smooth muscle specific MR in kidney injury and proteinuria is not known. Hence, we hypothesized that deficiency of endothelial and smooth muscle specific MRs (ECMRKO and SMMRKO) will protect the mice from Western diet-fed (high fat/high sucrose, WD) kidney injury and proteinuria. We fed female ECMRKO/SMMRKO and their littermate controls WD for 16wks and collected urine and performed imaging, molecular and morphological analyses. We observed significantly less proteinuria in the ECMRKO mice fed WD when compared to their littermates (2.4mg/mg vs. 3.5mg/mg creatinine) (p<0.05), however there was no change in the SMMRKO mice fed a WD when compared to their littermates. Furthermore, we observed significantly less impairment in aortic/renal pulse wave velocity and stiffness in both the ECMRKO/SMMRKO models. Western blots showed that there was a tendency to suppression of MR protein in the ECMRKO on WD. This suppression of MR expression was contemporaneously observed with decreased phosphorylation of ribosomal protein S6 along with reduction in membrane localization suggesting endothelial MR may regulate S6 activation. In summary, our study suggests endothelial specific MR may mediate kidney injury in conditions of MR activation and a lesser role for smooth muscle specific MR.

scholarly journals Adipose Tissue Hypoxia Correlates with Adipokine Hypomethylation and Vascular Dysfunction

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1034
Author(s):  
Mohamed M. Ali ◽  
Chandra Hassan ◽  
Mario Masrur ◽  
Francesco M. Bianco ◽  
Dina Naquiallah ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adipose Tissue ◽  
Cardiometabolic Risk ◽  
Vascular Dysfunction ◽  
Hypoxia Inducible Factor ◽  
Tissue Hypoxia ◽  
Cardiometabolic Risk Factors ◽  
Adipose Tissues ◽  
Obese Subjects

Obesity is characterized by the accumulation of dysfunctional adipose tissues, which predisposes to cardiometabolic diseases. Our previous in vitro studies demonstrated a role of hypoxia in inducing adipokine hypomethylation in adipocytes. We sought to examine this mechanism in visceral adipose tissues (VATs) from obese individuals and its correlation with cardiometabolic risk factors. We propose an involvement of the hypoxia-inducible factor, HIF1α, and the DNA hydroxymethylase, TET1. Blood samples and VAT biopsies were obtained from obese and non-obese subjects (n = 60 each) having bariatric and elective surgeries, respectively. The analyses of VAT showed lower vascularity, and higher levels of HIF1α and TET1 proteins in the obese subjects than controls. Global hypomethylation and hydroxymethylation were observed in VAT from obese subjects along with promoter hypomethylation of several pro-inflammatory adipokines. TET1 protein was enriched near the promotor of the hypomethylated adipokines. The average levels of adipokine methylation correlated positively with vascularity and arteriolar vasoreactivity and negatively with protein levels of HIF1α and TET1 in corresponding VAT samples, serum and tissue inflammatory markers, and other cardiometabolic risk factors. These findings suggest a role for adipose tissue hypoxia in causing epigenetic alterations, which could explain the increased production of adipocytokines and ultimately, vascular dysfunction in obesity.

scholarly journals Assessment of vascular function in formerly pre-eclamptic women as a novel marker of future cardiovascular risk

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
E Faes ◽  
D Mannaerts ◽  
I Witvrouwen ◽  
A Van Berendoncks ◽  
Y Jacquemyn ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Vascular Function ◽  
Pulse Wave ◽  
Augmentation Index ◽  
Vascular Dysfunction ◽  
Post Partum ◽  
Later Life ◽  
Low Flow ◽  
Healthy Controls ◽  
Increased Risk

Abstract Funding Acknowledgements Type of funding sources: None. Background Women with a history of pre-eclampsia (PE) are at increased risk of cardiovascular disease (CVD). The association between PE and CVD in later life may be explained by vascular dysfunction, either pre-existing or elicited by PE.  Several small studies have shown that vascular dysfunction may persist for years in some patients, indicator of future CVD risk, while other studies could not confirm these findings. Purpose In this longitudinal prospective cohort study, we aim to comprehensively assess vascular function in previously pre-eclamptic women (early (&lt;34 weeks) and late (&gt;34 weeks)) and healthy controls. We hypothesize that vascular dysfunction is both more persistent and pronounced in early PE compared to late PE since different pathophysiologic mechanisms underlie both subtypes of PE. Methods For this first analysis, 63 PE patients were compared to 16 non-pregnant healthy controls.  Endothelial function was determined by flow-mediated dilatation (FMD), modified FMD (mFMD) and low-flow mediated constriction (L-FMC). Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV) and augmentation index using pulse wave analysis of the brachial artery, and corrected for heart-rate (Aix75). Results Average post-partum period was 11 months (1.4-111.5 months). Thirty-five presented with early PE, 28 with late PE. In the total PE group, FMD was significantly decreased compared to healthy controls (7.1 ± 2.8 vs 8.9 ± 3.8; p = 0.037), but no difference between early and late PE was observed. Likewise, Aix75 remained elevated after PE (16.5 ± 11.5 vs 5.8 ± 10.1; p &lt; 0.001), again, without difference between early and late PE.  cfPWV was not different after PE compared to healthy controls (p &gt; 0.05) but was significantly higher in the early PE group compared to the late PE group (6.9 ± 1.0 vs 6.4 ± 1.0;  p = 0.045). Conclusion Even in the postpartum, PE is characterized by overt and persisting endothelial dysfunction and arterial stiffness. Arterial stiffness is more pronounced in early PE compared to late PE. This reaffirms that PE has consequences beyond placental impairment and that the persisting vascular impairment in the postpartum could reflect the risk of CVD later in life.

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