scholarly journals Endothelial Cell Indoleamine 2, 3-Dioxygenase 1 Alters Cardiac Function Following Myocardial Infarction Through Kynurenine

Circulation ◽  
2020 ◽  
Author(s):  
Nada Joe Melhem ◽  
Mouna Chajadine ◽  
Ingrid Gomez ◽  
Kiave-Yune Howangyin ◽  
Marion Bouvet ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Cardiac Function ◽  
Smooth Muscle Cells ◽  
Ventricular Remodeling ◽  
Muscle Cells ◽  
Protective Effects ◽  
Indoleamine 2

Background: Ischemic cardiovascular diseases, particularly acute myocardial infarction (MI) is one of the leading cause of mortality worldwide. Indoleamine 2, 3-dioxygenase 1 (IDO) catalyzes one rate-limiting step of L-Tryptophan (Trp) metabolism, and emerges as an important regulator of many pathological conditions. We hypothesized that IDO could play a key role to locally regulate cardiac homeostasis after MI. Methods: Cardiac repair was analyzed in mice harboring specific endothelial or smooth muscle cells or cardiomyocyte or myeloid cell deficiency of IDO and challenged with acute myocardial infarction. Results: We show that Kynurenine (Kyn) generation through IDO is markedly induced after MI in mice. Total genetic deletion or pharmacological inhibition of IDO limits cardiac injury and cardiac dysfunction after MI. Distinct loss of function of IDO in smooth muscle cells, inflammatory cells, or cardiomyocytes does not impact cardiac function and remodeling in infarcted mice. In sharp contrast, mice harboring endothelial cell-specific deletion of IDO show an improvement of cardiac function, as well as cardiomyocyte contractility and reduction in adverse ventricular remodeling. In vivo Kyn supplementation in IDO-deficient mice abrogates the protective effects of IDO deletion. Notably, Kyn precipitates cardiomyocyte apoptosis through reactive oxygen species production in an aryl hydrocarbon receptor-dependent mechanism. Conclusions: These data suggest that IDO could constitute a new therapeutic target during acute MI.

The serum protein fetuin-B is involved in the development of acute myocardial infarction

2015 ◽  
Vol 129 (1) ◽  
pp. 27-38 ◽  
Author(s):  
Seung Hyo Jung ◽  
Kyung-Jong Won ◽  
Kang Pa Lee ◽  
Hyun-Joong Kim ◽  
Eun-Hye Seo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Serum Protein ◽  
Vascular Smooth Muscle Cells ◽  
Stable Angina ◽  
Serum Proteins ◽  
Muscle Cells

Fetuin-B was one of highly expressed serum proteins in AMI compared with stable angina. This protein affected vascular plaque-stabilizing components in monocytes, macrophages and vascular smooth muscle cells. Fetuin-B may be a possible contributor to AMI.

scholarly journals Transcriptome alterations of vascular smooth muscle cells in aortic wall of myocardial infarction patients

Data in Brief ◽  
2018 ◽  
Vol 17 ◽  
pp. 1112-1135 ◽  
Author(s):  
Thidathip Wongsurawat ◽  
Chin Cheng Woo ◽  
Antonis Giannakakis ◽  
Xiao Yun Lin ◽  
Esther Sok Hwee Cheow ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Aortic Wall ◽  
Muscle Cells

The Role of Endothelial Cell Injury and Platelet Response in Atherogenesis

1977 ◽  
Author(s):  
L. A. Harker ◽  
R. Ross ◽  
J. Glomset
Keyword(s):  
Smooth Muscle ◽  
Endothelial Cell ◽  
Connective Tissue ◽  
Smooth Muscle Cells ◽  
Lipid Accumulation ◽  
Blood Platelets ◽  
Muscle Cells ◽  
Endothelial Injury ◽  
Intimal Proliferation ◽  
Flowing Blood

Endothelium forms a resistant barrier between flowing blood and vessel wall structures. Endothelial thromboresistance is maintained in part by the synthesis of prostacyclin, a potent prostaglandin inhibitor of platelet function. Loss of endothelial cells, mediated by physical, chemical, infectious or immune mechanisms, exposes the sub endothelium to flowing blood. Platelets react to the subendothelial connective tissue structures, undergoing adhesion and release of intracellular constituents, including a factor that is mitogenic to smooth muscle cells. This growth factor is a heat stable, basic protein (IP 7.4–9.4) of 20,000 Daltons and appears to be responsible for the intimal proliferation of smooth muscle cells that follows endothelial cell desquamation. After a single injury event the intimal lesion regresses over several months. Repeated or continuous endothelial cell loss results in progressive intimal proliferation of smooth muscle cells, their secretion of connective tissue matrix components (collagen, elastin and proteoglycans) and accumulation of lipid when animals are on a hypercholesterolemic diet to form early atherosclerotic intimal lesions. Discontinuance of endothelial injury and restoration of the endothelium appear to be followed by lesion regression except when lipid accumulation is extensive. Possible approaches to atherosclerosis prevention include: 1) protection of the endothelium by interruption or avoidance of endothelial injury factors, and perhaps by pharmacologic protection; 2) inhibition of platelet reactivity; 3) modification of SMC proliferation, secretion or lipid accumulation.

Electrical activation of endothelium evokes vasodilation and hyperpolarization along hamster feed arteries

2001 ◽  
Vol 280 (1) ◽  
pp. H160-H167 ◽  
Author(s):  
Geoffrey G. Emerson ◽  
Steven S. Segal
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Smooth Muscle Cells ◽  
Cell Damage ◽  
Muscle Cells ◽  
Sympathetic Nerves ◽  
Retractor Muscle ◽  
Receptor Interactions ◽  
Feed Arteries

Endothelial cells are considered electrically unexcitable. However, endothelium-dependent vasodilators (e.g., acetylcholine) often evoke hyperpolarization. We hypothesized that electrical stimulation of endothelial cells could evoke hyperpolarization and vasodilation. Feed artery segments (resting diameter: 63 ± 1 μm; length 3–4 mm) of the hamster retractor muscle were isolated and pressurized to 75 mmHg, and focal stimulation was performed via microelectrodes positioned across one end of the vessel. Stimulation at 16 Hz (30–50 V, 1-ms pulses, 5 s) evoked constriction (−20 ± 2 μm) that spread along the entire vessel via perivascular sympathetic nerves, as shown by inhibition with tetrodotoxin, ω-conotoxin, or phentolamine. In contrast, stimulation with direct current (30 V, 5 s) evoked vasodilation (16 ± 2 μm) and hyperpolarization (11 ± 1 mV) of endothelial and smooth muscle cells that conducted along the entire vessel. Conducted responses were insensitive to preceding treatments, atropine, or N ω-nitro-l-arginine, yet were abolished by endothelial cell damage (with air). Injection of negative current (≤1.6 nA) into a single endothelial cell reproduced vasodilator responses along the entire vessel. We conclude that, independent of ligand-receptor interactions, endothelial cell hyperpolarization evokes vasodilation that is readily conducted along the vessel wall. Moreover, electrical events originating within a single endothelial cell can drive the relaxation of smooth muscle cells throughout the entire vessel.

Various cells release a stable small molecule that inhibits endothelium-dependent relaxation

1995 ◽  
Vol 269 (4) ◽  
pp. H1303-H1311
Author(s):  
J. J. Liu ◽  
B. Xie ◽  
P. J. Thurlow ◽  
J. S. Wiley ◽  
J. R. Chen
Keyword(s):  
Smooth Muscle ◽  
Endothelial Cell ◽  
Tumor Cell ◽  
Smooth Muscle Cells ◽  
Cell Line ◽  
Tumor Cell Line ◽  
Muscle Cells ◽  
Cardiac Cells ◽  
Endothelial Cell Line ◽  
Endothelium Dependent Relaxation

Previous studies have shown that neutrophils release a stable factor that inhibits endothelium-dependent relaxation. In the present studies, the effects of supernatants derived from various cells on endothelium-dependent relaxation were studied. Cells were obtained from seven sources: human hematopoietic cells including mononuclear leukocytes (MONO), polymorphonuclear leukocytes (PMNs), and chronic lymphocytic leukemia (CLL) cells; cells of the cardiovascular system including human endothelial cell line ECV304, human smooth muscle cells, and rat myocardial cells; and the tumor cell line HPB. These isolated or cultured cells were incubated for 1 h in Krebs solution to release the factor. The results showed that the supernatants from 10(5) cells/ml of all cells except the tumor cell line HPB produced a potent inhibitory effect on endothelium-dependent relaxation of rat aortic rings in response to acetylcholine and Ca2+ ionophores A23187 and ionomycin but not on endothelium-independent relaxation to nitroprusside and glyceryl trinitrate. When the concentration increased to 10(6) cell/ml, the supernatants from the tumor cell line HPB also slightly but significantly inhibited endothelium-dependent relaxation. The potency order was PMNs = MONO = CLL cells > cardiac cells > smooth muscle cells > the endothelial cell line ECV304 > the tumor cell line HPB. It seems that the hematopoietic cells and the cardiac cells are more active in release of the factor. The effect of this factor was rapid in onset and hard to wash out. A cyclooxygenase inhibitor or a thromboxane A2-prostaglandin H2 receptor antagonist partially but significantly reduced the effect of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)

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