scholarly journals Obesity-induced vascular dysfunction and arterial stiffening requires endothelial cell arginase 1

2017 ◽  
Vol 113 (13) ◽  
pp. 1664-1676 ◽  
Author(s):  
Anil Bhatta ◽  
Lin Yao ◽  
Zhimin Xu ◽  
Haroldo A. Toque ◽  
Jijun Chen ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Vascular Dysfunction ◽  
Arterial Stiffening ◽  
Arginase 1

Abstract P217: Mitochondrial N-Formyl Peptides Elicit Changes in Endothelial Cell Cytoskeleton via Formyl Peptide Receptor Activation

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Camilla F Wenceslau ◽  
Cameron G McCarthy ◽  
R.Clinton Webb
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vascular Dysfunction ◽  
Receptor Activation ◽  
Vascular Leakage ◽  
Formyl Peptide Receptor ◽  
Experimental Hypertension ◽  
Peptide Receptor ◽  
Formyl Peptide ◽  
Formyl Peptides

One major pathophysiological characteristic of cardiovascular disease, including hypertension, is vascular dysfunction. Recently, we demonstrated that mitochondrial damage-associated molecular patterns are elevated in the circulation of SHR. Mitochondria carry hallmarks of their bacterial ancestry and one of these hallmarks is that this organelle still uses an N-formyl-methionyl-tRNA as an initiator of protein synthesis. We observed that mitochondrial N-formyl peptides (F-MIT) infusion into rats induces inflammation and vascular dysfunction, including vascular leakage, via formyl peptide receptor (FPR) activation. However, neutrophil depletion did not change this response. Therefore, we hypothesize that F-MIT via FPR activation elicits changes directly to cytoskeleton-regulating proteins in vascular cells, which may lead to increased vascular permeability. To test this hypothesis we used vascular smooth muscle cells (VSMC) and endothelial cells harvested from aortas of Sprague-Dawley rats (n=5) and human donors (n=5), respectively. Cells were divided into three groups for Western blot analysis of cytoskeleton-regulating proteins. The cells were incubated for 20 minutes in medium with either vehicle (non-formylated peptide), F-MIT (10 μM), or F-MIT after a 5-minute pre-incubation with FPR1 and 2 antagonists (Cyclosporine H, CsH, 1 μM and WRW4, 10 μM). In endothelial cells, the treatment with F-MIT increased the protein expression of RhoA/ROCK (Rho: 1.8 fold vs. Veh; ROCK: 1.4 fold vs. Veh, p<0.05), cell division control protein 42 (CDC42) (2.0 fold vs. Veh, p<0.05) and phospho-myosin light chain (MLC) Thr/Ser19 (1.5 fold vs. Veh, p<0.05). These changes were all abolished in the presence of FPR antagonists. On the other hand, F-MIT decreased expression of phospho-MLC (0.6 fold vs. Veh, p<0.05) and CDC42 (0.5 fold vs. Veh, p<0.05) and did not change RhoA/ROCK expression in VSMC. In conclusion, F-MIT, via FPR activation, elicits direct changes in endothelial cell and VSMC cytoskeleton-regulating proteins. This interaction can lead to endothelial contraction, increased vascular leakage and attenuated barrier function as observed in clinical and experimental hypertension.

Preconditioning and adenosine in I/R-induced leukocyte-endothelial cell interactions

1998 ◽  
Vol 274 (4) ◽  
pp. H1230-H1238 ◽  
Author(s):  
Paul Kubes ◽  
Derrice Payne ◽  
Lena Ostrovsky
Keyword(s):  
Endothelial Cell ◽  
Leukocyte Adhesion ◽  
Vascular Dysfunction ◽  
Ischemia Reperfusion ◽  
Microvascular Dysfunction ◽  
Cell Interactions ◽  
Minor Role ◽  
Neutrophil Adhesion ◽  
Rolling Velocity

Recently, it was reported that preconditioning reduced leukocyte adhesion following ischemia-reperfusion (I/R). We further examined the effects of preconditioning and adenosine not only on neutrophil adhesion but also on neutrophil rolling and vascular dysfunction. Intravital microscopy revealed a decrease in neutrophil rolling velocity; a profound increase in neutrophil rolling, adhesion, and microvascular dysfunction; and a reduction in venular shear rates associated with 60 min ischemia and 60 min reperfusion in the feline mesentery. Preconditioning (5 min ischemia/10 min reperfusion) prevented subsequent I/R-induced slow neutrophil rolling, neutrophil adhesion, and microvascular dysfunction but did not affect the flux of rolling neutrophils. Adenosine deaminase A1and A2adenosine-receptor antagonists had only minor effects on the preconditioning responses. Pretreatment of vessels with exogenous adenosine reduced neutrophil adhesion and microvascular permeability and improved neutrophil rolling velocity and shear forces associated with I/R, but the flux of rolling neutrophils was not affected. Finally, in vitro experiments revealed that adenosine had absolutely no direct effect on neutrophil-endothelial cell interactions. In conclusion, our data suggest that adenosine plays only a minor role in preconditioned vessels and that adenosine per se may not directly affect neutrophil-endothelial cell interactions.

scholarly journals HuangqiGuizhiWuwu Decoction Prevents Vascular Dysfunction in Diabetes via Inhibition of Endothelial Arginase 1

2020 ◽  
Vol 11 ◽  
Author(s):  
Hong Cheng ◽  
Tian Lu ◽  
Jingya Wang ◽  
Yucen Xia ◽  
Xiaoshu Chai ◽  
...  
Keyword(s):  
Vascular Dysfunction ◽  
Arginase 1

scholarly journals Acute e-cig inhalation impacts vascular health: a study in smoking naïve subjects

2021 ◽  
Vol 320 (1) ◽  
pp. H144-H158
Author(s):  
Shampa Chatterjee ◽  
Alessandra Caporale ◽  
Jian Qin Tao ◽  
Wensheng Guo ◽  
Alyssa Johncola ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Signaling ◽  
Vascular Dysfunction ◽  
Healthy Adults ◽  
Vascular Health ◽  
Vascular Changes ◽  
Blood Biomarkers ◽  
Single Episode

Endothelial cell signaling and blood biomarkers were found to correlate with functional vascular changes in a single episode e-cigarettes inhalation in healthy adults. This is indicative of the potential of e-cigarettes (even when inhaled acutely) to lead of vascular dysfunction.

scholarly journals Extracellular histones induce calcium signals in the endothelium of resistance-sized mesenteric arteries and cause loss of endothelium-dependent dilation

2019 ◽  
Vol 316 (6) ◽  
pp. H1309-H1322 ◽  
Author(s):  
Daniel M. Collier ◽  
Nuria Villalba ◽  
Adrian Sackheim ◽  
Adrian D. Bonev ◽  
Zachary D. Miller ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Transient Receptor Potential ◽  
Prolonged Exposure ◽  
Vascular Dysfunction ◽  
Receptor Potential ◽  
Mesenteric Arteries ◽  
Transient Receptor Potential Vanilloid ◽  
Histone Proteins ◽  
Genetic Ablation ◽  
Channel Inhibition

Histone proteins are elevated in the circulation after traumatic injury owing to cellular lysis and release from neutrophils. Elevated circulating histones in trauma contribute to coagulopathy and mortality through a mechanism suspected to involve endothelial cell (EC) dysfunction. However, the functional consequences of histone exposure on intact blood vessels are unknown. Here, we sought to understand the effects of clinically relevant concentrations of histones on the endothelium in intact, resistance-sized, mesenteric arteries (MAs). EC Ca2+ was measured with high spatial and temporal resolution in MAs from mice selectively expressing the EC-specific, genetically encoded ratiometric Ca2+ indicator, Cx40-GCaMP-GR, and vessel diameter was measured by edge detection. Application of purified histone protein directly to the endothelium of en face mouse and human MA preparations produced large Ca2+ signals that spread within and between ECs. Surprisingly, luminal application of histones had no effect on the diameter of pressurized arteries. Instead, after prolonged exposure (30 min), it reduced dilations to endothelium-dependent vasodilators and ultimately caused death of ~25% of ECs, as evidenced by markedly elevated cytosolic Ca2+ levels (793 ± 75 nM) and uptake of propidium iodide. Removal of extracellular Ca2+ but not depletion of intracellular Ca2+ stores prevented histone-induced Ca2+ signals. Histone-induced signals were not suppressed by transient receptor potential vanilloid 4 (TRPV4) channel inhibition (100 nM GSK2193874) or genetic ablation of TRPV4 channels or Toll-like receptor receptors. These data demonstrate that histones are robust activators of noncanonical EC Ca2+ signaling, which cause vascular dysfunction through loss of endothelium-dependent dilation in resistance-sized MAs. NEW & NOTEWORTHY We describe the first use of the endothelial cell (EC)-specific, ratiometric, genetically encoded Ca2+ indicator, Cx40-GCaMP-GR, to study the effect of histone proteins on EC Ca2+ signaling. We found that histones induce an influx of Ca2+ in ECs that does not cause vasodilation but instead causes Ca2+ overload, EC death, and vascular dysfunction in the form of lost endothelium-dependent dilation.

scholarly journals Endothelial cell senescence in aging-related vascular dysfunction

2019 ◽  
Vol 1865 (7) ◽  
pp. 1802-1809 ◽  
Author(s):  
Guanghong Jia ◽  
Annayya R. Aroor ◽  
Cassie Jia ◽  
James R. Sowers
Keyword(s):  
Endothelial Cell ◽  
Vascular Dysfunction ◽  
Cell Senescence

scholarly journals Intravascular Hemolysis Leads to Priapism Phenotype: Experimental Evidence

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1076-1076
Author(s):  
Fabio H Silva ◽  
Beatriz Pereira Bossarino ◽  
Fabiano B Calmasini ◽  
Eduardo Costa Alexandre ◽  
Fernando F. Costa
Keyword(s):  
Nitric Oxide ◽  
Conflicts Of Interest ◽  
Vascular Dysfunction ◽  
Corpus Cavernosum ◽  
Electrical Field Stimulation ◽  
Control Group ◽  
Intravascular Hemolysis ◽  
Nitric Oxide Signaling ◽  
Plasma Hemoglobin ◽  
Arginase 1

Abstract Introduction: Sickle cell disease (SCD) men display priapism. Berkeley and Townes SCD transgenic mice also display priapism phenotype associated with increased corpus cavernosum relaxation. Primary mechanism underlying priapism appears to be due to reduced nitric oxide bioavailability, which leads to downregulation of phosphodiesterase type 5 (PDE5) in the penis. Previous clinical studies reported that priapism is associated with increased intravascular hemolysis at SCD. Intravascular hemolysis releases components that impair nitric oxide signaling, such as hemoglobin, asymmetric dimethylarginine and arginase-1. It is well-established that nitric oxide scavenging by cell-free hemoglobin contributes to vascular dysfunction. However, no detailed study has investigated the role of intravascular hemolysis on pathophysiological alterations of erectile function. Since intravascular hemolysis can influence the biological activity of nitric oxide pathway, we hypothesized that excess concentration of plasma hemoglobin may contribute to priapism in SCD. Therefore, in the present study, we have used a murine model of intravascular hemolysis induced by phenylhydrazine (PHZ) to evaluate the effects of intravascular hemolysis on the nitric oxide-mediated corpus cavernosum relaxations. Methods: Intravascular hemolysis was induced in C57BL/6 mice by intraperitoneal injection of PHZ. C57BL/6 mice were injected with PHZ at 50 mg/Kg and then reinjected with 50 mg/Kg 8h later. Mice were killed in isoflurane chamber at 2 days after the first injection with PHZ. Strips of corpus cavernosum were mounted in isolated organ baths, and the relaxing responses to acetylcholine (ACh; endothelium-dependent response) and sodium nitroprusside (SNP; endothelium-independent response), as well as electrical-field stimulation (EFS; nitrergic relaxation) were obtained in corpus cavernosum strips precontracted with the α1-adrenergic receptor agonist phenylephrine (10 µM). Results: Plasma hemoglobin was significantly higher in PHZ compared to control mice (11±1 and 4±1 µM, respectively; P<0.001), which demonstrate the increase in the rate of intravascular hemolysis in PHZ-treated animals. The cumulative addition of ACh (0.001-10 µM) produced concentration-dependent corpus cavernosum relaxations in both groups, but maximal relaxations were significantly higher in PHZ (59±4 %; P<0.05, n=7) compared to control mice (45±4%). Likewise, SNP (0.01-10 µM) produced concentration-dependent corpus cavernosum relaxations, but, again, the maximal relaxations induced by this agent were significantly higher in PHZ (87±2%, P<0.01) compared to the control group (74±1%, n=7). Similarly, the nitrergic relaxations caused by EFS were also significantly higher (P<0.05) in PHZ mice compared to control mice (32 Hz: 79±2 and 66± 1%, respectively; n=5). Conclusion: Our study shows that intravascular hemolysis leads to increased nitric oxide-mediated cavernosal relaxations, indicating that PHZ mice exhibit priapism phenotype. It is likely that hemoglobin act to inactivate nitric oxide, thus reducing the amount of bioavailable nitric oxide, which may lead to downregulation of PDE5 in the penis. One may speculate, therefore, that the reduced degradation of cGMP by PDE5 in PHZ mice may lead to the enhancement of nitric oxide-mediated cavernosal relaxations. To confirm this hypothesis, we will evaluate the expression of PDE5 and cGMP levels in PHZ mice penises. Financial Support: FAPESP. Disclosures No relevant conflicts of interest to declare.

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