Neuropeptide Y and its receptors in ventricular endocardial endothelial cells

2017 ◽  
Vol 95 (10) ◽  
pp. 1224-1229 ◽  
Author(s):  
Danielle Jacques ◽  
Pedro D’Orléans-Juste ◽  
Sheldon Magder ◽  
Ghassan Bkaily
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Cardiac Function ◽  
Neuropeptide Y ◽  
Entry And Exit ◽  
Cardiac Pathology ◽  
Contraction Coupling ◽  
Endocardial Endothelial Cells ◽  
The Right ◽  
Cardiac Excitation

Endocardial endothelial cells (EECs) constitute an important component of the heart. These cells form a monolayer that covers the cavities of the right (EECRs) and left (EECLs) ventricles. They play an important role in cardiac excitation–contraction coupling via their secretion of cardioactive factors such as neuropeptide Y (NPY). They also contribute to cardiac pathology such as arrhythmia, hypertrophy, and heart failure. Differences between EECRs and EECLs contribute to tuning of circulating factors at the entry and exit of the ventricles. NPY, via activation of its receptors, modulates the excitation–secretion coupling of EECs, thus, indirectly modulating cardiac function and remodeling.

scholarly journals Chronic Benzene Exposure Aggravates Pressure Overload-Induced Cardiac Dysfunction

2021 ◽  
Author(s):  
Igor N Zelko ◽  
Sujith Dassanayaka ◽  
Marina V Malovichko ◽  
Caitlin M Howard ◽  
Lauren F Garrett ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Cardiac Function ◽  
Cardiac Tissue ◽  
Pressure Overload ◽  
Endothelial Activation ◽  
Air Exposure ◽  
Benzene Exposure ◽  
Increased Risk

Benzene is a ubiquitous environmental pollutant abundant in household products, petrochemicals and cigarette smoke. Benzene is a well-known carcinogen in humans and experimental animals; however, little is known about the cardiovascular toxicity of benzene. Recent population-based studies indicate that benzene exposure is associated with an increased risk for heart failure. Nonetheless, it is unclear whether benzene exposure is sufficient to induce and/or exacerbate heart failure. We examined the effects of benzene (50 ppm, 6 h/day, 5 days/week, 6 weeks) or HEPA-filtered air exposure on transverse aortic constriction (TAC)-induced pressure overload in male C57BL/6J mice. Our data show that benzene exposure had no effect on cardiac function in the Sham group; however, it significantly compromised cardiac function as depicted by a significant decrease in fractional shortening and ejection fraction, as compared with TAC/Air-exposed mice. RNA-seq analysis of the cardiac tissue from the TAC/benzene-exposed mice showed a significant increase in several genes associated with adhesion molecules, cell-cell adhesion, inflammation, and stress response. In particular, neutrophils were implicated in our unbiased analyses. Indeed, immunofluorescence studies showed that TAC/benzene exposure promotes infiltration of CD11b+/S100A8+/myeloperoxidase+-positive neutrophils in the hearts by 3-fold. In vitro, the benzene metabolites, hydroquinone and catechol, induced the expression of P-selectin in cardiac microvascular endothelial cells by 5-fold and increased the adhesion of neutrophils to these endothelial cells by 1.5-2.0-fold. Benzene metabolite-induced adhesion of neutrophils to the endothelial cells was attenuated by anti-P-selectin antibody. Together, these data suggest that benzene exacerbates heart failure by promoting endothelial activation and neutrophil recruitment.

Oxidative stress induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure

2008 ◽  
Vol 104 (3) ◽  
pp. 307-320 ◽  
Author(s):  
Giampiero Rocca ◽  
Antonino Stefano ◽  
Ermanno Eleuteri ◽  
Rita Anzalone ◽  
Francesca Magno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Endothelial Cells ◽  
Chronic Heart Failure ◽  
Endocardial Endothelial Cells

The neuropeptide galanin promotes an anti-thrombotic phenotype on endocardial endothelial cells from heart failure patients

2017 ◽  
Vol 206 ◽  
pp. 35-42 ◽  
Author(s):  
Christina Tyrrell ◽  
Amanda Toyooka ◽  
Faiza Khan ◽  
Kent L. Thornburg ◽  
James O. Mudd ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Heart Failure Patients ◽  
Endocardial Endothelial Cells

scholarly journals Gut-Derived Metabolite Indole-3-Propionic Acid Modulates Mitochondrial Function in Cardiomyocytes and Alters Cardiac Function

2021 ◽  
Vol 8 ◽  
Author(s):  
Maren Gesper ◽  
Alena B. H. Nonnast ◽  
Nina Kumowski ◽  
Robert Stoehr ◽  
Katharina Schuett ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Fatty Acid ◽  
Cardiac Function ◽  
Mitochondrial Dysfunction ◽  
Propionic Acid ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Acid Oxidation ◽  
Microbial Metabolites

Background: The gut microbiome has been linked to the onset of cardiometabolic diseases, in part facilitated through gut microbiota-dependent metabolites such as trimethylamine-N-oxide. However, molecular pathways associated to heart failure mediated by microbial metabolites remain largely elusive. Mitochondria play a pivotal role in cellular energy metabolism and mitochondrial dysfunction has been associated to heart failure pathogenesis. Aim of the current study was to evaluate the impact of gut-derived metabolites on mitochondrial function in cardiomyocytes via an in vitro screening approach.Methods: Based on a systematic Medline research, 25 microbial metabolites were identified and screened for their metabolic impact with a focus on mitochondrial respiration in HL-1 cardiomyocytes. Oxygen consumption rate in response to different modulators of the respiratory chain were measured by a live-cell metabolic assay platform. For one of the identified metabolites, indole-3-propionic acid, studies on specific mitochondrial complexes, cytochrome c, fatty acid oxidation, mitochondrial membrane potential, and reactive oxygen species production were performed. Mitochondrial function in response to this metabolite was further tested in human hepatic and endothelial cells. Additionally, the effect of indole-3-propionic acid on cardiac function was studied in isolated perfused hearts of C57BL/6J mice.Results: Among the metabolites examined, microbial tryptophan derivative indole-3-propionic acid could be identified as a modulator of mitochondrial function in cardiomyocytes. While acute treatment induced enhancement of maximal mitochondrial respiration (+21.5 ± 7.8%, p < 0.05), chronic exposure led to mitochondrial dysfunction (−18.9 ± 9.1%; p < 0.001) in cardiomyocytes. The latter effect of indole-3-propionic acids could also be observed in human hepatic and endothelial cells. In isolated perfused mouse hearts, indole-3-propionic acid was dose-dependently able to improve cardiac contractility from +26.8 ± 11.6% (p < 0.05) at 1 μM up to +93.6 ± 14.4% (p < 0.001) at 100 μM. Our mechanistic studies on indole-3-propionic acids suggest potential involvement of fatty acid oxidation in HL-1 cardiomyocytes.Conclusion: Our data indicate a direct impact of microbial metabolites on cardiac physiology. Gut-derived metabolite indole-3-propionic acid was identified as mitochondrial modulator in cardiomyocytes and altered cardiac function in an ex vivo mouse model.

Differences in neuropeptide Y-induced secretion of endothelin-1 in left and right human endocardial endothelial cells

Neuropeptides ◽  
2012 ◽  
Vol 46 (6) ◽  
pp. 373-382 ◽  
Author(s):  
Dima Abdel-Samad ◽  
Claudine Perreault ◽  
Lena Ahmarani ◽  
Levon Avedanian ◽  
Ghassan Bkaily ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neuropeptide Y ◽  
Endothelin 1 ◽  
Left And Right ◽  
Endocardial Endothelial Cells

Targeting Altered Calcium Physiology in the Heart: Translational Approaches to Excitation, Contraction, and Transcription

Physiology ◽  
2007 ◽  
Vol 22 (5) ◽  
pp. 328-334 ◽  
Author(s):  
Tim Seidler ◽  
Gerd Hasenfuss ◽  
Lars S. Maier
Keyword(s):  
Heart Failure ◽  
Signal Transduction ◽  
Physiological Function ◽  
Signaling Proteins ◽  
Transcriptional Responses ◽  
Cardiac Growth ◽  
Cardiac Pathology ◽  
Contraction Coupling ◽  
And Function ◽  
Ca Homeostasis

Calcium (Ca) is essential for excitation-contraction coupling. At the same time, Ca is of pivotal importance as a second messenger in cardiac signal transduction, where it regulates cardiac growth and function by activation of kinases and phosphatases, ultimately driving transcriptional responses and feeding back on Ca handling proteins, a phenomenon termed excitation-transcription coupling. Cardiac Ca homeostasis thus needs to be maintained via a delicate interplay of proteins to allow physiological function and adaptation, whereas disturbed Ca-handling and Ca-dependent signaling are hallmarks of heart failure. In this review, we will discuss the most recent mechanistic findings in Ca-handling and Ca-signaling proteins in the development of cardiac pathology with a focus on translational aspects.

scholarly journals Homeostasis Regulating Factors, Innervation, Ischemia and Inflammatory Markers in the Right Atrial Tissue from Patients with Degenerative Aortic Valve Stenosis and Coronary Heart Disease

2021 ◽  
Vol 75 (3) ◽  
pp. 186-193
Author(s):  
Edīte Vārtiņa ◽  
Māra Pilmane ◽  
Romāns Lācis
Keyword(s):  
Coronary Heart Disease ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Inflammatory Markers ◽  
Chromogranin A ◽  
Right Atrial ◽  
Pgp 9.5 ◽  
Atrial Tissue ◽  
Endocardial Endothelial Cells ◽  
The Right

Abstract Both coronary heart disease (CHD) and degenerative aortic valve (AoV) stenosis have common risk factors, such as age, high blood cholesterol, diabetes, smoking, high blood pressure, inflammation, and metabolic syndrome. However, these diseases are not always observed together, confirming the existence of risk and pathogenesis factors specific to each disease. The aim of this study was to identify presence and distribution of common and different homeostasis regulating factors, innervation, ischemia and inflammatory markers in the right atrial tissue from patients with degenerative AoV stenosis and CHD. During elective cardiac surgery, right atrial tissue fragments were taken from 20 patients with CHD and from 9 patients with degenerative AoV stenosis. All tissue fragments were stained for immunohistochemical detection of protein-gene peptide 9.5 (PGP 9.5), atrial natriuretic peptide (ANUP), vascular endothelial growth factor (VEGF), chromogranin A, endothelin, interleukin 1 and 10 (Il-1 and Il-10) and β defensins 2, and 3 (βD2 and βD3). For the quantification of structures, a semi-quantitative counting method was used. Mostly numerous Il-10 positive cardiomyocytes and epi-/endocardial endothelial cells were detected in all specimens taken from patients with CHD, and statistically more than in specimens taken from patients with degenerative AoV disease (p = 0.007 and p = 0.016). Also, the number of βD3 positive cardiomyocytes was higher in the coronary heart disease group (p = 0.026). All other tested markers such as PGP 9.5, ANUP, VEGF, endothelin, chromogranin A, Il-1 and βD2 showed similar expression in both groups. Increased production of ANUP in right atrial tissue characterises both CHD and degenerative AoV stenosis. Production of ChgA in right atrial endocardial endothelial cells might represent regulation of sympathetic activity as a compensatory homeostatic response. Increased PGP 9.5-containing innervation is characteristic in patients with degenerative AoV disease and secondary mitral insufficiency. A stable increase of VEGF and variations of endothelin without statistically significant difference suggest influence of ischemia on the local vascular blood supply. Decreased production of Il-1α together with moderate to rich production of Il-10, βD2, and βD3 indicates the dominance of the local immune system over inflammation.

scholarly journals Cardiac-specific deletion of voltage dependent anion channel 2 leads to dilated cardiomyopathy by altering calcium homeostasis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Thirupura S. Shankar ◽  
Dinesh K. A. Ramadurai ◽  
Kira Steinhorst ◽  
Salah Sommakia ◽  
Rachit Badolia ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Calcium Signaling ◽  
Calcium Homeostasis ◽  
Anion Channel ◽  
Calcium Dynamics ◽  
Voltage Dependent Anion Channel ◽  
Contraction Coupling ◽  
Voltage Dependent

AbstractVoltage dependent anion channel 2 (VDAC2) is an outer mitochondrial membrane porin known to play a significant role in apoptosis and calcium signaling. Abnormalities in calcium homeostasis often leads to electrical and contractile dysfunction and can cause dilated cardiomyopathy and heart failure. However, the specific role of VDAC2 in intracellular calcium dynamics and cardiac function is not well understood. To elucidate the role of VDAC2 in calcium homeostasis, we generated a cardiac ventricular myocyte-specific developmental deletion of Vdac2 in mice. Our results indicate that loss of VDAC2 in the myocardium causes severe impairment in excitation-contraction coupling by altering both intracellular and mitochondrial calcium signaling. We also observed adverse cardiac remodeling which progressed to severe cardiomyopathy and death. Reintroduction of VDAC2 in 6-week-old knock-out mice partially rescued the cardiomyopathy phenotype. Activation of VDAC2 by efsevin increased cardiac contractile force in a mouse model of pressure-overload induced heart failure. In conclusion, our findings demonstrate that VDAC2 plays a crucial role in cardiac function by influencing cellular calcium signaling. Through this unique role in cellular calcium dynamics and excitation-contraction coupling VDAC2 emerges as a plausible therapeutic target for heart failure.

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