scholarly journals Role of S100A4 in atherosclerosis development

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L M Cardoso Dos Santos ◽  
N Ambartsumian ◽  
M Grigorian ◽  
M L Bochaton-Piallat
Keyword(s):  
National Budget ◽  
Funding Sources ◽  
S100a4 Expression ◽  
Marker Expression ◽  
Atherosclerosis Development ◽  
Differentiation Marker ◽  
Public Grant

Abstract Background Smooth muscle cells (SMCs) accumulate into the intima during the process of atherosclerosis, where they switch from a contractile to a synthetic phenotype. We previously identified S100A4 as being a marker of the synthetic SMCs. Recently we have shown that extracellular S100A4 induces a pro-inflammatory-like SMC phenotype and is causally related to atherosclerotic plaque progression. Aim To study the role of intracellular S100A4 depletion in the SMC phenotypic transition during atherosclerosis. Methods We used a full S100A4 knockout (KO) mouse model, where we performed left common carotid ligation and collected carotid arteries after 4 weeks. Primary SMCs were cultured from wild type (WT) and KO animals. We investigated differentiation marker expression, NFκB activation with extracellular S100A4, proliferation and migratory capacities. Results are given as mean ± SD (Fig. 1A and B). Results In vivo, no difference in intimal thickening (IT) size and SMC differentiation marker expression was observed between WT and S100A4 KO mice. CD68 was absent and S100A4 was only detected in WT animals in the inner layer of the IT. In vitro, no difference in differentiation marker expression, proliferation (Fig. 1A) or NFκB activation (Fig. 1C) was observed. Interestingly, migration was decreased in the absence of S100A4 (Fig. 1B) Conclusion The in vivo abrogation of S100A4 does not interfere with IT progression, suggesting that the lack of inflammation in this model might render S100A4 expression neglectable and disguise a possible effect of S100A4 depletion in IT progression. In vitro, S100A4 plays a role in SMC migration. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation Figure 1

scholarly journals Introducing Gordonibacter urolithinfaciens into Gut Ecosystems to Study Its Role in Mediating the Metabolic Benefits of Dietary Polyphenols

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1594-1594
Author(s):  
Ashley Toney ◽  
Yibo Xian ◽  
Jing Shao ◽  
Robert Schmaltz ◽  
Virginia Chaidez ◽  
...  
Keyword(s):  
Drinking Water ◽  
Ellagic Acid ◽  
Improve Insulin Sensitivity ◽  
Microbial Conversion ◽  
Dietary Polyphenols ◽  
Funding Sources ◽  
Host Metabolism

Abstract Objectives Dietary polyphenols such as ellagitannins undergo microbial conversion to yield urolithins, which improve insulin sensitivity. However, feeding ellagic acid-containing foods sometimes yields variable levels of metabolic improvements in humans, suggesting that some individuals may not harbor the specific microbes responsible for transforming ellagic acid (EA) into urolithins. One species of gut bacteria, Gordonibacter urolithinfaciens (G. uro), has been shown to convert EA into urolithins in vitro. However, the specific role of G. uro in mediating the metabolic benefits of EA-containing foods in vivo is unknown, in part, because of challenges associated with its engraftment in mouse models. This study aimed to determine whether G. uro could be introduced into an established microbiota as a single dose or daily probiotic to facilitate future studies regarding its role in improving host metabolism via conversion of EA to urolithins. Methods Germ-free (GF) C57BL/6 mice were either: (1) mono-associated with G. uro for 2 wks prior to introduction of one of three conventional mouse microbiotas naturally deficient for G. uro, (2) colonized with both G. uro and a conventional G. uro-deficient microbiota together, (3) colonized with a conventional G. uro-deficient microbiota for 2 wks and then given a single oral gavage of G. uro, or (4) colonized with a conventional G. uro-deficient microbiota for 2 wks and then administered G. uro fresh daily in drinking water. Results G. uro successfully monocolonized a previously GF mouse but was not detectable following introduction of a complex G. uro-deficient microbiota. G. uro also failed to persist when GF mice were first colonized with a conventional G. uro-deficient microbiota and then given a single gavage of G. uro. However, ex-GF mice colonized with a complex G. uro-deficient microbiota and given daily doses of G. uro in their drinking water were able to maintain this organism throughout the study. Conclusions Our studies demonstrate the challenges associated with introducing G. uro into a microbiota even when G. uro is provided prior to microbiota establishment and the microbiota is naturally devoid of G. uro. These results suggest that G. uro may need to be administered as a daily probiotic to provide health benefits to individuals unable to convert ellagic acid foods into beneficial urolithins. Funding Sources USDA NIFA.

PDE4B and PDE4D differentially regulate cardiac pacemaker activity

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
WPV Pereira De Vasconcelos ◽  
AMG Gomez ◽  
RF Fischmeister ◽  
GV Vandecasteele ◽  
DM Mika
Keyword(s):  
Ventricular Myocytes ◽  
Cardiac Pacemaker ◽  
Hydrolytic Activity ◽  
Pde4 Inhibitor ◽  
Pacemaker Activity ◽  
National Budget ◽  
Beating Rate ◽  
Public Grant

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Agence Nationale de la Recherche (ANR) Background Heart rate (HR) is generated by spontaneous electrical activity in the sinoatrial node (SAN) and is modulated by the autonomic nervous system. During sympathetic stimulation, the activation of β-adrenergic receptors (βAR) increases cAMP levels, leading to positive chronotropic effect. Among the 6 cardiac cAMP-PDE families, PDE4 is critical for controlling excitation-contraction coupling (ECC) during β-stimulation in atrial and ventricular myocytes. PDE4 may also be important for automaticity. 3 genes encode for PDE4 in the heart (pde4a, 4b, 4d). We propose to investigate their respective contribution to the regulation of pacemaker activity.  Methods Total PDE activity in mouse SAN was determined as the cAMP-hydrolytic activity measured in the absence of PDE inhibitor and the fraction corresponding to PDE4 activity was assessed by including the PDE4 inhibitor Ro-20-1724. The in vitro pacemaker activity was assessed by measuring spontaneous Ca2+ transients in Fluo4-loaded-SAN tissue from wild-type (WT) and PDE4KO mice. Images were obtained using confocal microscopy. Telemetry EKG was recorded in conscious mice in control (CTRL) conditions, after pharmacological denervation with atropine (1 mg/kg) and propranolol (2 mg/kg) and after β-stimulation with isoproterenol (ISO, 1.5 mg/kg). HR variability was evaluated by calculating the SDNN (standard deviation of RR intervals) parameter. Results Ro-20-1724 (10 µM) increased beating rate of intact SAN and increased PKA-phosphorylation of key ECC actors (ryanodine receptor, phospholamban and contractile proteins). PDE4 activity was found to account for 60% of total cAMP-PDE activity in SAN. PDE4A, 4B and 4D isoforms were found to be expressed in mouse SAN. In PDE4BKO SAN, the effect of ISO on SAN beating rate was higher than in WT. Ablation of PDE4D induced decreased beating rate in CTRL and ISO conditions and increased Ca2+ spark frequency compared to WT SAN. In vivo, PDE4BKO and PDE4DKO mice displayed increased resting HR during day and night. HR variability was decreased in PDE4BKO, but not in PDE4DKO mice during the day, and decreased in both genotypes at night compared to WT mice. After atropine + propranolol denervation, the rhythmic phenotype was only maintained in PDE4BKO but not in PDE4DKO mice. The response to β-AR stimulation with ISO was higher in PDE4BKO than in PDE4DKO. In addition, under ISO we observed an increased number of premature beats and atrioventricular blocks in PDE4DKO, but not in PDE4BKO mice. Conclusion PDE4B and PDE4D differentially regulate cardiac pacemaker activity. While PDE4B clearly controls intrinsic SAN automaticity, PDE4D might be important for ANS-mediated regulation of HR and conduction.

scholarly journals The role of circumferential strain in the differential diagnosis of cardiomyopathies with left ventricular hypertrabeculation

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Szucs ◽  
ZS Gregor ◽  
AR Kiss ◽  
M Horvath ◽  
V Farsang ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Circumferential Strain ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Lv Function ◽  
National Budget ◽  
Funding Sources ◽  
Innovation And Technology ◽  
Public Grant

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Supported by the ÚNKP-19-3-II New National Excellence Program of the Ministry for Innovation and Technology Dilated (DCM), hypertrophic (HCM) and noncompaction cardiomyopathy (NCMP) are genetically and morphologically overlapping diseases, however they differ in clinical manifestation, treatment and prognosis. Cardiac MRI feature-tracking might help to differentiate between these cardiomyopathies with left ventricular (LV) hypertrabeculation. We aimed to describe the differences in the functional and strain parameters of NCMP patients with good LV ejection fraction (EF, NCMP-G) compared with patients with HCM, and NCMP patients with reduced EF (NCMP-R) compared with patients with DCM . We included 62 NCMP patients from which 31 had good LV function and 31 had decreased LV-EF. The NCMP-G group was compared with an HCM population (n = 31) and the NCMP-R group was compared with a DCM group (n = 31) matching in age and sex (age, EF; NCMP-G 46.0 ± 13.0 years, 65.5 ± 5.3% vs. HCM 47.2 ± 14.4 years, 74.8 ± 6.3%; NCMP-R 54.5 ± 12.1 years, 32.8 ± 10.1% vs. DCM 50.8 ± 16.7 years, 34.0 ± 8.2%).  1.5 T Philips Achieva and Siemens Aera MRI machines were used for the scans, Medis Suite program was used for analysis and MedCalc software for statistics, p < 0.05 was considered statistically significant. Significant differences were found between the functional parameters of HCM and NCMP-G patients, while the DCM and NCMP-R groups differed only in the trabecular mass values (LV-trab, NCMP-G vs. HCM: 26.2 ± 7.5 vs. 30.7 ± 7.0 g/m2, NCMP-R vs. DCM:  48.2 ± 13.2 vs. 42.1 ± 10.1 g/m2, p < 0.05). The global longitudinal strain values of the studied populations were not significantly different, however the global circumferential strain (GCS) values were significantly better in patients with HCM and DCM compared with the NCMP groups (GCS, NCMP-G vs. HCM: -31.2 ± 4.9 vs. -43.0 ± 8.4%, NCMP-R vs. DCM: -11.7 ± 7.3 vs. -16.9 ± 6.1%). The average circumferential strain values of the LV basal, mid and apical parts were significantly better in the HCM and DCM groups compared with the NCMP groups (NCMP-G vs. HCM: -35.7 ± 9.5 vs. -50.5 ± 14.1%, NCMP-R vs. DCM: -29.5 ± 13.2 vs. -15.6 ± 6,7%).  We assessed the cut-off point of the average LV apical circumferential strain to differentiate the studied populations (HCM vs. NCMP-G cut-off: -47.3% sens.: 83.9%, spec.: 67.7%, AUC: 0.81; DCM vs. NCMP-R cut-off: -19.3% sens.: 83.9%, spec.: 83.9%, AUC: 0.86). The diverse circumferential strain values of the hypertrabeculated LV apical third could help the differential diagnosis of NCMP, DCM and HCM.

scholarly journals Relation of biomarkers of inflammation, oxidative stress and fibrosis in patient with atrial fibrillation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
P Pauklin ◽  
J Eha ◽  
M Zilmer ◽  
K Tootsi ◽  
M Kals ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Atrial Fibrillation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
National Budget ◽  
Funding Sources ◽  
Markers Of Inflammation ◽  
Public Grant

Abstract Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice. The patogenesis of AF is linked to an inflammatory reaction and oxidative stress that leads to fibrosis of the atria and progression of the disease. However, the role of different biomarkers in patients with AF is poorly defined. The purpose of this study is to define the role of several biomarkers of inflammation, oxidative stress and fibrosis (myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), galectin-3 (Gal-3), oxidized low-density lipoprotein (oxLDL)) in patients with AF. Methods We included 75 patients with paroxysmal/persistent AF, who were admitted for electrical cardioversion or pulmonary vein isolation. MPO, hsCRP, Gal-3 and oxLDL were measured before the procedures. We compared the results with 75 healthy age-, sex- and blood pressure-matched individuals. Results Patients with AF had higher MPO (77.1 vs 41.7 ng/ml, p<0.001) compared the healthy subjects. There was also significantly higher hsCRP (3.7 vs 1.6 mg/L, p<0.001) and Gal-3 (12.3 vs 10.4 mg/L, p=0.003). No difference in oxLDL levels (78.8 vs 75.3 U/L, p=0.414) were seen (Table 1). MPO (β=0.012, p=0.014), hsCRP (β=0.213, p=0.046), and weight (β=0.037, p=0.006), were independently associated with AF in a logistic regression analysis (Table 2). Conclusions Patients with AF have increased markers of inflammation and fibrosis, whereas no increase in oxidative stress markers was detected. MPO, hsCRP and age weight were independently predictive of AF. These findings support the role of inflammatory and fibrotic mechanisms as important factors in the electrical and structural remodelling progress in the atria of patients with AF. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Estonian Research Council

scholarly journals The m6A methyltransferase METTL3 promotes hypoxic pulmonary arterial hypertension via targeting PTEN

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Q I N Yuhan ◽  
T A N G Chengchun
Keyword(s):  
Pulmonary Arteries ◽  
Rna Modification ◽  
Funding Sources ◽  
Pten Mrna ◽  
Rna Immunoprecipitation ◽  
M6a Rna Methylation ◽  
And Migration

Abstract Background N6-methyladenosine (m6A) is the most prevalent internal RNA modification in mammal mRNAs. Accumulating evidence has indicated the crucial role of m6A modification in cardiovascular diseases including cardiac hypertrophy, heart failure, ischemic heart disease, vascular calcification, restenosis, and aortic aneurysm. However, the role of m6A methylation in the occurrence and development of hypoxic pulmonary hypertension (HPH) remains largely unknown. Purpose The present study aims to explore the role of key transferase METTL3, in the development of HPH. Methods Hypoxic rat models and pulmonary artery smooth muscle cells (PASMCs) and were used to research the METTL3-mediated m6A in HPH in vivo and in vitro. CCK-8, EdU, PCNA, transwell and TUNEL assay were performed to evaluate the proliferation, migration and apoptosis rates of PASMCs. m6A RNA Methylation Quantification Kit and m6A-qPCR were utilized to measure the total m6A level and m6A-PTEN mRNA expression. RNA immunoprecipitation and RNA pull down were used to detect the interaction between METTL3 and PTEN mRNA. The half-life of mRNA was detected through actinomycin D assay. Results Both METTL3 mRNA and protein were found abnormally upregulated in pulmonary arteries of HPH rats and hypoxia induced PASMCs. Furthermore, downregulation of METTL3 attenuated PASMCs proliferation and migration exposed to hypoxia. In addition, m6A binding protein YTHDF2 was found significantly increased in HPH group in vivo and in vitro. Mechanistically, YTHDF2 recognized METTL3 mediated m6A-PTEN mRNA and promoted the degradation of PTEN. Decreased PTEN led to over-proliferation of PASMCs through activation of PI3K/Akt signaling pathway. Conclusion METTL3/YTHDF2/PTEN axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for HPH. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): National Natural Science Foundation of China Figure 1

scholarly journals Beyond Self-Recycling: Cell-Specific Role of Autophagy in Atherosclerosis

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 625
Author(s):  
James M. Henderson ◽  
Christian Weber ◽  
Donato Santovito
Keyword(s):  
Cell Types ◽  
Chronic Inflammatory Disease ◽  
In Vivo Studies ◽  
Cell Type ◽  
Therapeutic Implications ◽  
Atherosclerosis Development ◽  
Specific Deletion

Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall and underlies the development of cardiovascular diseases, such as myocardial infarction and ischemic stroke. As such, atherosclerosis stands as the leading cause of death and disability worldwide and intensive scientific efforts are made to investigate its complex pathophysiology, which involves the deregulation of crucial intracellular pathways and intricate interactions between diverse cell types. A growing body of evidence, including in vitro and in vivo studies involving cell-specific deletion of autophagy-related genes (ATGs), has unveiled the mechanistic relevance of cell-specific (endothelial, smooth-muscle, and myeloid cells) defective autophagy in the processes of atherogenesis. In this review, we underscore the recent insights on autophagy’s cell-type-dependent role in atherosclerosis development and progression, featuring the relevance of canonical catabolic functions and emerging noncanonical mechanisms, and highlighting the potential therapeutic implications for prevention and treatment of atherosclerosis and its complications.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Anti-obesity role of Aster glehni extract: in vivo and in vitro effects

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
HM Lee ◽  
TG Ahn ◽  
CW Kim ◽  
HJ An
Keyword(s):  
In Vitro Effects

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

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