scholarly journals Autoantibodies Targeting AT1 Receptor from Patients with Acute Coronary Syndrome Upregulate Proinflammatory Cytokines Expression in Endothelial Cells Involving NF-κB Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Weijuan Li ◽  
Zhi Li ◽  
Yaoqi Chen ◽  
Songhai Li ◽  
Yuanyuan Lv ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Proinflammatory Cytokines ◽  
At1 Receptor ◽  
Neonatal Rat ◽  
Pyrrolidine Dithiocarbamate ◽  
Mobility Shift ◽  
Rat Cardiomyocytes ◽  
Protein Levels ◽  
Coronary Syndrome ◽  
Chemotactic Protein

Our study intended to prove whether agonistic autoantibodies to angiotensin II type 1 receptor (AT1-AAs) exist in patients with coronary heart disease (CHD) and affect the human endothelial cell (HEC) by upregulating proinflammatory cytokines expression involved in NF-κB pathway. Antibodies were determined by chronotropic responses of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists (valsartan and AT1-EC2) as described previously. Interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemotactic protein-1 (MCP-1) expression were improved at both mRNA and protein levels in HEC, while NF-κB in the DNA level was improved detected by electrophoretic mobility shift assays (EMSA). These improvements could be inhibited by specific AT1 receptor blocker valsartan, NF-κB blocker pyrrolidine dithiocarbamate (PDTC), and specific short peptides from the second extracellular loop of AT1 receptor. These results suggested that AT1-AAs, via the AT1 receptor, induce expression of proinflammatory cytokines involved in the activation of NF-κB. AT1-AAs may play a great role in the pathogenesis of the acute coronary syndrome by mediating vascular inflammatory effects involved in the NF-κB pathway.

Brain-derived neurotrophic factor is associated with coronary macrophage infiltrates in patients with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R.A Montone ◽  
M Camilli ◽  
M Russo ◽  
M Del Buono ◽  
F Gurguglione ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Neurotrophic Factor ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
C Reactive Protein ◽  
St Segment Elevation ◽  
Protein Levels ◽  
Reactive Protein ◽  
Coronary Syndrome ◽  
St Segment

Abstract Background Brain-derived neurotrophic factor (BDNF) is a neurotrophine that plays a key role in the regulation of both central and peripheral nervous system. Moreover, BDNF is secreted in multiple tissues and exerts systemic, autocrine, and paracrine effects in the cardiovascular system. Of importance, BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries and may be involved in thrombus formation. Thus, BDNF has been suggested as an important link between inflammation and thrombosis, potentially involved in the pathogenesis of acute coronary syndrome (ACS). Purpose In our study we aimed at assessing serum levels of BDNF in patients with ACS, evaluating differences according to clinical presentation [ST-segment elevation myocardial infarction (STEMI) vs. Non-ST-segment elevation ACS (NSTE-ACS)]. Moreover, we assessed the presence of optical coherence (OCT)-defined macrophage infiltrates (MØI) in the culprit vessel of ACS patients and evaluated their relationship with BDNF levels. Methods ACS patients were prospectively selected. Blood samples were collected at admission and serum levels of BDNF were subsequently assessed. Presence of OCT-defined MØI along the culprit vessel was assessed. Results 166 ACS patients were enrolled [mean age 65.3±11.9 years, 125 (75.3%) male, 109 STEMI, 57 NSTE-ACS]. Serum levels of BDNF were higher among STEMI patients compared with NSTE-ACS [median (IQR) 2.48 pg/mL (1.54–3.34) vs. 2.12 pg/mL (1.34–2.47), p=0.007], while C-reactive protein levels did not differ between the two groups. OCT assessment was performed in 53 patients and MØI were detected in 27 patients. Of importance, patients with MØI in the culprit vessel had higher levels of BDNF compared with patients without MØI [median (IQR) 2.23 pg/mL (1.38–2.53) vs. 1.41 pg/mL (0.93–2.07), p=0.023], while C-reactive protein levels did not differ between the two groups. Of note, at multivariate regression analysis BDNF levels were independent predictor of MØI [OR: 2.20; 95% CI (1.02–4.74), p=0.043]. Conclusions Serum levels of BDNF may reliable identify the presence of local macrophage inflammatory infiltrates in patients with ACS. Moreover, BDNF levels are higher in patients with STEMI compared with NSTE-ACS. Taken together, these data suggest that BDNF may represent an interesting link between local inflammatory activation and enhanced thrombosis in ACS. BDNF serum levels Funding Acknowledgement Type of funding source: None

scholarly journals Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1667
Author(s):  
Jian-Hong Lin ◽  
Kun-Ta Yang ◽  
Pei-Ching Ting ◽  
Yu-Po Luo ◽  
Ding-Jyun Lin ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Acetic Acid ◽  
Ischemia Reperfusion ◽  
Neonatal Rat ◽  
Mrna Levels ◽  
H9c2 Cells ◽  
Rat Cardiomyocytes ◽  
Protein Levels ◽  
Gossypol Acetic Acid

Myocardial ischemia/reperfusion (I/R) injury has been associated with ferroptosis, which is characterized by an iron-dependent accumulation of lipid peroxide to lethal levels. Gossypol acetic acid (GAA), a natural product taken from the seeds of cotton plants, prevents oxidative stress. However, the effects of GAA on myocardial I/R-induced ferroptosis remain unclear. This study investigated the ability of GAA to attenuate I/R-induced ferroptosis in cardiomyocytes along with the underlying mechanisms in a well-established rat model of myocardial I/R and isolated neonatal rat cardiomyocytes. H9c2 cells and cardiomyocytes were treated with the ferroptosis inducers erastin, RSL3, and Fe-SP. GAA could protect H9c2 cells against ferroptotic cell death caused by these ferroptosis inducers by decreasing the production of malondialdehyde and reactive oxygen species, chelating iron content, and downregulating mRNA levels of Ptgs2. GAA could prevent oxygen-glucose deprivation/reperfusion-induced cell death and lipid peroxidation in the cardiomyocytes. Moreover, GAA significantly attenuated myocardial infarct size, reduced lipid peroxidation, decreased the mRNA levels of the ferroptosis markers Ptgs2 and Acsl4, decreased the protein levels of ACSL4 and NRF2, and increased the protein levels of GPX4 in I/R-induced ex vivo rat hearts. Thus, GAA may play a cytoprotectant role in ferroptosis-induced cardiomyocyte death and myocardial I/R-induced ferroptotic cell death.

cAMP modulates glucocorticoid-induced protein accumulation and glucocorticoid receptor in cardiomyocytes

1996 ◽  
Vol 271 (5) ◽  
pp. E827-E833 ◽  
Author(s):  
A. Sato ◽  
K. E. Sheppard ◽  
M. J. Fullerton ◽  
J. W. Funder
Keyword(s):  
Glucocorticoid Receptor ◽  
Second Messengers ◽  
Muscle Growth ◽  
Inhibitory Effect ◽  
Neonatal Rat ◽  
Protein Accumulation ◽  
Rat Cardiomyocytes ◽  
Cyclic Monophosphate ◽  
Protein Levels

Glucocorticoids have complex effects on cardiac muscle growth in vivo, and one possible reason may the regulatory cross talk between glucocorticoids and second messengers. In this study we investigated the effect of adenosine 3',5'-cyclic monophosphate (cAMP), shown to affect cardiomyocyte growth and glucocorticoid action in several systems, on glucocorticoid-induced protein accumulation and glucocorticoid receptor (GR) in neonatal rat cardiomyocytes. Dexamethasone (DEX) decreased the protein-to-DNA ratio, and 8-bromoadenosine 3',5'-cyclic monophosphate (BrcAMP) or forskolin increased this ratio. The inhibitory effect of DEX was potentiated by an elevated cAMP, despite the stimulatory effect of cAMP alone. Nuclear GR binding was increased by BrcAMP, with no change in GR mRNA or protein levels, via increased affinity of nuclear GR. H-89 blocked the effects of BrcAMP. In conclusion, glucocorticoids have an inhibitory effect on protein accumulation in cardiomyocytes via GR, an effect potentiated by elevated cAMP via increased nuclear GR binding. These results suggest that glucocorticoid effects on cardiomyocytes may be modulated by cAMP-mediated mechanisms, which may produce the complex effects of glucocorticoids on cardiomyocyte growth in vivo.

scholarly journals Lycopene Inhibits Urotensin-II-Induced Cardiomyocyte Hypertrophy in Neonatal Rat Cardiomyocytes

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Hung-Hsing Chao ◽  
Li-Chin Sung ◽  
Cheng-Hsien Chen ◽  
Ju-Chi Liu ◽  
Jin-Jer Chen ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Activity Level ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Urotensin Ii ◽  
Rat Cardiomyocytes ◽  
Protein Levels ◽  
Neonatal Rat Cardiomyocytes ◽  
Tensin Homolog

This study investigated how lycopene affected urotensin-II- (U-II-) induced cardiomyocyte hypertrophy and the possible implicated mechanisms. Neonatal rat cardiomyocytes were exposed to U-II (1 nM) either exclusively or following 6 h of lycopene pretreatment (1–10 μM). The lycopene (3–10 μM) pretreatment significantly inhibited the U-II-induced cardiomyocyte hypertrophy, decreased the production of U-II-induced reactive oxygen species (ROS), and reduced the level of NAD(P)H oxidase-4 expression. Lycopene further inhibited the U-II-induced phosphorylation of the redox-sensitive extracellular signal-regulated kinases. Moreover, lycopene treatment prevented the increase in the phosphorylation of serine-threonine kinase Akt and glycogen synthase kinase-3beta (GSK-3β) caused by U-II without affecting the protein levels of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN). However, lycopene increased the PTEN activity level, suggesting that lycopene prevents ROS-induced PTEN inactivation. These findings imply that lycopene yields antihypertrophic effects that can prevent the activation of the Akt/GSK-3βhypertrophic pathway by modulating PTEN inactivation through U-II treatment. Thus, the data indicate that lycopene prevented U-II-induced cardiomyocyte hypertrophy through a mechanism involving the inhibition of redox signaling. These findings provide novel data regarding the molecular mechanisms by which lycopene regulates cardiomyocyte hypertrophy.

scholarly journals The -844 G>A PAI-1 Polymorphism Is Associated with Acute Coronary Syndrome in Mexican Population

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ilian Janet García-González ◽  
Yeminia Valle ◽  
Elena Sandoval-Pinto ◽  
Emmanuel Valdés-Alvarado ◽  
Angélica Valdez-Haro ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Plasminogen Activator Inhibitor ◽  
Recessive Model ◽  
High Morbidity ◽  
Plasminogen Activator Inhibitor 1 ◽  
Protein Levels ◽  
Western Mexico ◽  
Coronary Syndrome ◽  
Genetic Distribution ◽  
Pai 1

Background. Acute coronary syndrome (ACS) has an important impact in public health with high morbidity and mortality. Prothrombotic and proinflammatory states are involved in the pathogenesis of the disease. Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of the fibrinolysis and also is part of immune response. The -844 G>A gene polymorphism is related to increased PAI-1 protein levels. The aim of the study is to evaluate the association of -844 G>A PAI-1 polymorphism with ACS.Methods. A total of 646 individuals were recruited from Western Mexico: 350 unrelated healthy subjects and 296 patients with diagnosis of ACS.Results. The most important risk factor in our population was hypertension, followed by smoking. The genetic distribution showed an association of the A allele (OR=1.27,P=0.04) and AA genotype (OR=1.86,P=0.02) with ACS. The recessive model displayed similar results (OR=1.76,P=0.02). As additional finding, we observed significant differences in the genetic distribution of ACS dyslipidemic patients (OR=1.99,P=0.04). The A allele and AA genotype of -844 polymorphism of PAI-1 gene are risk factors for ACS. The AA genotype might be associated with the development of dyslipidemia in ACS patients.

scholarly journals A STUDY OF C-REACTIVE PROTEIN LEVELS IN ACUTE CORONARY SYNDROME AND A CORRELATION WITH THE OUTCOME

2017 ◽  
Vol 6 (18) ◽  
pp. 1417-1420
Author(s):  
Umamaheshwari S ◽  
Vishwanatha Huggi ◽  
Mahesh Menon ◽  
Arunkumar Arunkumar ◽  
Sireesh Kumar
Keyword(s):  
Acute Coronary Syndrome ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein ◽  
Coronary Syndrome

scholarly journals Urocortin induces interleukin-6 release from rat cardiomyocytes through p38 MAP kinase, ERK and NF-κB activation

2009 ◽  
Vol 42 (5) ◽  
pp. 397-405 ◽  
Author(s):  
Man Huang ◽  
Duraisamy Kempuraj ◽  
Nikoletta Papadopoulou ◽  
Taxiarchis Kourelis ◽  
Jill Donelan ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Map Kinases ◽  
P38 Map Kinase ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
P38 Inhibitor ◽  
Coronary Syndrome ◽  
Neonatal Rat Cardiomyocytes ◽  
Dose Dependent Fashion

CRH and its structurally related peptide urocortin (Ucn) are released under stress. Ucn is a potent agonist for CRH-receptor 2 (CRH-R2), which is strongly expressed in rodent heart. Stress induces Ucn mRNA expression in the heart, where it may be cardioprotective. However, increasing evidence indicates that Ucn may also have pro-inflammatory actions. Here, we show that neonatal rat cardiomyocytes express CRH-R2 by western blot analysis and Ucn induces interleukin-6 (IL-6) release in a time- and dose-dependent fashion. Ucn stimulates activation of ERK and p38 MAP kinases, while both MEK1 and p38 inhibitor block Ucn-induced IL-6 release. Ucn also activates nuclear factor kappa B (NF-κB) and a NF-κB inhibitor blocks Ucn-induced IL-6 release. Finally, the CRH-R antagonists α-helical (9–41) CRH and astressin-2B completely inhibit Ucn-induced IL-6 release, as well as activation of ERK, p38, and NF-κB. These findings indicate that Ucn induces IL-6 synthesis and release from neonatal rat cardiomyocytes. Our findings suggest that even though Ucn may confirm some protection on cardiomyocyte survival, it can also release IL-6, which is an independent risk factor for acute coronary syndrome. The precise role of cardiac Ucn in vivo remains to be elucidated.

Regulation of NHE-1 promoter in mammalian myocardium

1996 ◽  
Vol 270 (1) ◽  
pp. H259-H266 ◽  
Author(s):  
W. Yang ◽  
J. R. Dyck ◽  
H. Wang ◽  
L. Fliegel
Keyword(s):  
Mammalian Cells ◽  
Ph Regulation ◽  
Integral Membrane Protein ◽  
Neonatal Rat ◽  
Mobility Shift ◽  
Rat Cardiomyocytes ◽  
Nuclear Extracts ◽  
Mobility Shift Assay ◽  
Gel Mobility Shift ◽  
Reduced Activity

The Na+/H exchanger (NHE-1) is an integral membrane protein responsible for intracellular pH regulation in the myocardium and other tissues. The NHE-1 isoform is universally distributed in mammalian cells. We examined regulation of a 1.1-kb fragment of the NHE-1 promoter in neonatal rat cardiomyocytes. Deletion of most of the promoter up to an AP-2 site reduced activity 75%. Further deletion of the promoter or mutation of the AP-2 site reduced or eliminated activity almost completely. Gel mobility shift assay showed that purified AP-2 protein or AP-2-like protein from nuclear extracts of isolated myocytes can bind to DNA of the NHE-1 protein. External acidosis did not cause increased transcription from the promoter. Removal of serum from the medium reduced activity of the NHE-1 promoter. The elements responsible for activation of the promoter by serum were contained within both the 1.1-kb and AP-2-containing region. The results show that the cis-acting putative AP-2 site and the presence of serum are important in NHE-1 expression, whereas external acidosis had no direct effect on the promoter.

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