scholarly journals Vasorelaxing effects of estetrol in rat arteries

2012 ◽  
Vol 215 (1) ◽  
pp. 97-106 ◽  
Author(s):  
Rob H P Hilgers ◽  
Suzanne Oparil ◽  
Wout Wouters ◽  
Herjan J T Coelingh Bennink
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Soluble Guanylate Cyclase ◽  
Ex Vivo ◽  
Response Curves ◽  
Uterine Arteries ◽  
17Β Estradiol ◽  
Pharmacological Blockade ◽  
Relaxation Responses

This study comparedex vivorelaxing responses to the naturally occurring human hormone estetrol (E4) vs 17β-estradiol (E2) in eight different vascular beds. Arteries were mounted in a myograph, contracted with either phenylephrine or serotonin, and cumulative concentration-response curves (CRCs) to E4and E2(0.1–100 μmol/l) were constructed. In all arteries tested, E4had lower potency than E2, although the differential effect was less in larger than smaller arteries. In uterine arteries, the nonselective estrogen receptor (ER) blocker ICI 182 780 (1 μmol/l) caused a significant rightward shift in the CRC to both E4and E2, indicating that the relaxation responses were ER dependent. Pharmacological blockade of nitric oxide (NO) synthases byNω-nitro-l-arginine methyl ester (l-NAME) blunted E2-mediated but not E4-mediated relaxing responses, while inhibition of prostaglandins and endothelium-dependent hyperpolarization did not alter relaxation to either E4or E2in uterine arteries. Combined blockade of NO release and action withl-NAME and the soluble guanylate cyclase (sGC) inhibitor ODQ resulted in greater inhibition of the relaxation response to E4compared with E2in uterine arteries. Endothelium denudation inhibited responses to both E4and E2, while E4and E2concentration-dependently blocked smooth muscle cell Ca2+entry in K+-depolarized and Ca2+-depleted uterine arteries. In conclusion, E4relaxes precontracted rat arteries in an artery-specific fashion. In uterine arteries, E4-induced relaxations are partially mediated via an endothelium-dependent mechanism involving ERs, sGC, and inhibition of smooth muscle cell Ca2+entry, but not NO synthases or endothelium-dependent hyperpolarization.

Abstract 584: Smooth Muscle Cell-derived IL-17C Plays an Atherogenic Role via the Recruitment of Pro-inflammatory IL-17A + T Cells to the Aorta

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Matthew J Butcher ◽  
Tayab C Waseem ◽  
Elena V Galkina
Keyword(s):  
T Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Th17 Cells ◽  
Ex Vivo ◽  
Flow Cytometric Analysis ◽  
Atherosclerotic Lesion ◽  
Atherosclerotic Lesions

Atherosclerosis is characterized by frequent communication between infiltrating leukocytes and vascular cells, through chemokine and cytokine networks. IL-17 cytokine family members, including IL-17C, are detectable within atherosclerotic plaques, however the potential involvement of these cytokines have not been examined. Thus we sought to investigate the role of IL-17C in atherosclerosis. The expression of IL-17 cytokines was profiled within atherosclerotic Apoe -/- aortas and Il17c expression was elevated. Flow cytometry experiments revealed a major population of aortic IL-17C-producing smooth muscle cells. To determine the role of IL-17C in atherosclerosis, we generated Il17c -/- Apoe -/- mice and compared atherosclerotic lesions between western diet-fed Apoe -/- and Il17c -/- Apoe -/- mice. Atherosclerotic lesion and collagen content was diminished within WD-fed Il17c -/- Apoe -/- aortas and aortic roots in comparison to Apoe -/- controls, and IL-17C treated Apoe -/- aortas up-regulated Col1A1 expression ex vivo . Flow cytometric analysis of Il17c -/- Apoe -/- aortas revealed a proportional reduction in aortic leukocytes, macrophages, neutrophils, T cells, Th1, and T regulatory cells, without corresponding changes in the peripheral immune composition. Examination of aortic IL-17A + TCRγδ T cells and Th17 cells demonstrated a stark reduction in the percentage and number of these subsets within Il17c -/- Apoe -/- mice versus Apoe -/- controls. Explanted 12 week WD Apoe -/- aortas treated with IL-17C resulted in the induction of multiple vascular chemokines and cytokines, and short-term homing experiments revealed diminished recruitment of Th17 cells to the aorta of Il17c -/- Apoe -/- recipients. Smooth muscle cell-derived IL-17C plays a pro-atherogenic role by supporting the recruitment of Th17 cells to atherosclerotic lesions.

Effects of ultraviolet light in vascular cells in vitro and in intact atherosclerotic explants: potential role of apoptosis in vascular biology

1996 ◽  
Vol 74 (3) ◽  
pp. 333-345 ◽  
Author(s):  
Angel López-Candales ◽  
Michael J. Scott ◽  
Samuel A. Wickline ◽  
Dennis R. Holmes ◽  
Robert W. Thompson
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Short Wavelength ◽  
Ex Vivo ◽  
Zealand White Rabbit ◽  
Light Therapy ◽  
Vascular Cells

Complex cell-to-cell interactions are known to participate during vascular injury and remodeling, resulting in smooth muscle cell proliferation. Mechanical interventions have yielded little benefit in limiting this process and several site-specific genetic therapies are not yet clinically available. The aim of this study was to delineate the effect of very short wavelength ultraviolet (UVC) light therapy on the viability of macrophage and smooth muscle cells. Vascular cells were both treated in vitro and in intact explanted atherosclerotic aortic segments ex vivo with UVC light. Brief exposure to short wavelength UVC light in the absence of photosensitizers elicited a differential temporal and functional response among treated cells. However, dramatic reduction in both cellular viability and proliferative capacity with eventual cell demise was observed in all UVC-treated cells. Flow cytometry and immunohistochemical analyses revealed the presence of extensive DNA fragmentation, suggestive of apoptosis as a predominant pathway of cell death in these cells exposed to UVC light. We hypothesize that selective induction of apoptosis, in contrast to necrosis, with UVC light may represent a beneficial approach to interdict the complex biologic cascade of messengers that participate in the restenotic response to vascular injury.Key words: apoptosis, macrophage, smooth muscle cell, atherosclerotic aorta, New Zealand White rabbit.

scholarly journals Evaluation of Arteriolar Smooth Muscle Cell Function in an Ex Vivo Microvascular Network Model

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jessica M. Motherwell ◽  
Mohammad S. Azimi ◽  
Kristine Spicer ◽  
Natascha G. Alves ◽  
Nicholas A. Hodges ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Network Model ◽  
Muscle Cell ◽  
Cell Function ◽  
Ex Vivo ◽  
Microvascular Network

Endothelial and Smooth Muscle Cell Seeding onto Processed Ex Vivo Arterial Scaffolds Using 3D Vascular Bioreactors

ASAIO Journal ◽  
2004 ◽  
Vol 50 (6) ◽  
pp. 591-600 ◽  
Author(s):  
Peter S. McFetridge ◽  
Tulin Bodamyali ◽  
Michael Horrocks ◽  
Julian B. Chaudhuri
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Ex Vivo ◽  
Cell Seeding

scholarly journals Lack of tone in mouse small mesenteric arteries leads to outward remodeling, which can be prevented by prolonged agonist-induced vasoconstriction

2018 ◽  
Vol 315 (3) ◽  
pp. H644-H657 ◽  
Author(s):  
Anika Klein ◽  
Philomeena Daphne Joseph ◽  
Vibeke Grøsfjeld Christensen ◽  
Lars Jørn Jensen ◽  
Jens Christian Brings Jacobsen
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Cell Activation ◽  
Ex Vivo ◽  
Mesenteric Arteries ◽  
Similar Response ◽  
Resistance Vessels

Inward remodeling of resistance vessels is an independent risk factor for cardiovascular events. Thus far, the remodeling process remains incompletely elucidated, but the activation level of the vascular smooth muscle cell appears to play a central role. Accordingly, previous data have suggested that an antagonistic and supposedly beneficial response, outward remodeling, may follow prolonged vasodilatation. The present study aimed to determine whether 1) outward remodeling follows 3 days of vessel culture without tone, 2) a similar response can be elicited in a much shorter 4-h timeframe, and, finally, 3) whether a 4-h response can be prevented or reversed by the presence of vasoconstrictors in the medium. Cannulated mouse small mesenteric arteries were organocultured for 3 days in the absence of tone, leading to outward remodeling that continued throughout the culture period. In more acute experiments in which cannulated small mesenteric arteries were maintained in physiological saline without tone for 4 h, we detected a similar outward remodeling that proceeded at a rate several times faster. In the 4-h experimental setting, continuous vasoconstriction to ~50% tone by abluminal application of UTP or norepinephrine + neuropeptide Y prevented outward remodeling but did not cause inward remodeling. Computational modeling was used to simulate and interpret these findings and to derive time constants of the remodeling processes. It is suggested that depriving resistance arteries of activation will lead to eutrophic outward remodeling, which can be prevented by vascular smooth muscle cell activation induced by prolonged vasoconstrictor exposure. NEW & NOTEWORTHY We have established an effective 4-h method for studying outward remodeling in pressurized mouse resistance vessels ex vivo and have determined conditions that block the remodeling response. This allows for investigating the subtle but clinically highly relevant phenomenon of outward remodeling while avoiding both laborious 3-day organoid culture of cannulated vessels and in vivo experiments lasting several weeks.

scholarly journals Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity

2021 ◽  
Vol 22 (23) ◽  
pp. 12812
Author(s):  
Matthias Bosman ◽  
Dustin N. Krüger ◽  
Kasper Favere ◽  
Callan D. Wesley ◽  
Cédric H. G. Neutel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Arterial Stiffness ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Reactivity ◽  
Transient Receptor Potential ◽  
Ex Vivo ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels

Clinical and animal studies have demonstrated that chemotherapeutic doxorubicin (DOX) increases arterial stiffness, a predictor of cardiovascular risk. Despite consensus about DOX-impaired endothelium-dependent vasodilation as a contributing mechanism, some studies have reported conflicting results on vascular smooth muscle cell (VSMC) function after DOX treatment. The present study aimed to investigate the effects of DOX on VSMC function. To this end, mice received a single injection of 4 mg DOX/kg, or mouse aortic segments were treated ex vivo with 1 μM DOX, followed by vascular reactivity evaluation 16 h later. Phenylephrine (PE)-induced VSMC contraction was decreased after DOX treatment. DOX did not affect the transient PE contraction dependent on Ca2+ release from the sarcoplasmic reticulum (0 mM Ca2+), but it reduced the subsequent tonic phase characterised by Ca2+ influx. These findings were supported by similar angiotensin II and attenuated endothelin-1 contractions. The involvement of voltage-gated Ca2+ channels in DOX-decreased contraction was excluded by using levcromakalim and diltiazem in PE-induced contraction and corroborated by similar K+ and serotonin contractions. Despite the evaluation of multiple blockers of transient receptor potential channels, the exact mechanism for DOX-decreased VSMC contraction remains elusive. Surprisingly, DOX reduced ex vivo but not in vivo arterial stiffness, highlighting the importance of appropriate timing for evaluating arterial stiffness in DOX-treated patients.

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