239. Hormonal control of vascular mural cell recruitment in the mouse endometrium

2005 ◽  
Vol 17 (9) ◽  
pp. 94
Author(s):  
J. E. Girling ◽  
L. M. Walter ◽  
P. A. W. Rogers
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Hormonal Control ◽  
Specific Marker ◽  
Mural Cell ◽  
Physiological Basis ◽  
Oestrogen Treatment ◽  
Cell Recruitment ◽  
Progesterone Treatment ◽  
Vehicle Injection

The human endometrium undergoes regular periods of growth and regression, including concomitant changes in the vasculature, and is one of the few adult tissues where significant angiogenesis (new blood vessel formation) and arteriogenesis (recruitment of vascular smooth muscle cells (VSMC) and pericytes) occurs on a routine, physiological basis. In this study, mouse models were used to investigate the effects of oestrogen and progesterone on endometrial vascular mural cell recruitment. The aim was to quantify changes in the proportion of vessels covered by α-smooth muscle actin (α-SMA, a marker of VSMC and pericytes) in hormone-treated ovariectomised mice. We hypothesised that relative vessel α-SMA coverage would increase following progesterone treatment (in conjunction with endothelial cell (EC) proliferation), but not following oestrogen treatment (when EC proliferation also occurs). Ovariectomised mice were given a single oestradiol (100 ng) or vehicle injection, before dissection 24 h later, or three consecutive daily injections of progesterone (1 mg) or vehicle. The percentage of vessel profiles with no, minimal, extensive or complete α-SMA coverage were quantified after CD31/α-SMA double immunostaining. There was a significant decrease in the percentage of vessel profiles with no α-SMA coverage following progesterone treatment (20±4.3 % [mean±SE] v. 57±4.6 %, t(7)=12.5, P<0.001), and a significant increase in the percentage of vessels with minimal or extensive α-SMA coverage (44±3.4 % v. 27±3.7%, t(7)=4.7, P<0.001 and 27±4.3% v. 5±0.5%, t(7)=5.8, P<0.001, respectively), in comparison to vehicle-treated mice. The percentage of vessels with complete α-SMA coverage, representing vessels with a coat of VSMC, did not change significantly in comparison to vehicle-treated mice (8±2.3% v. 10±1.2%, t(7)=0.6, P=0.55). There were no significant changes in the percentage of vessels with differing α-SMA coverage in oestrogen-treated mice. In continuing studies, we will quantify the proportion of proliferating α-SMA positive cells and examine mouse endometrial tissues using a pericyte-specific marker.

scholarly journals Insights into cerebral haemodynamics and oxygenation utilising in vivo mural cell imaging and mathematical modelling

2017 ◽  
Author(s):  
Paul W. Sweeney ◽  
Simon Walker-Samuel ◽  
Rebecca J. Shipley
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Mathematical Modelling ◽  
Oxygen Transport ◽  
Muscle Activation ◽  
Smooth Muscle Actin ◽  
Blood Velocity ◽  
Mural Cell ◽  
Proxy Measurement

AbstractThe neurovascular mechanisms underpinning the local regulation of cerebral blood flow (CBF) and oxygen transport remain elusive. In this study we have combined novel in vivo imaging of cortical microvascular and mural cell architecture with mathematical modelling of blood flow and oxygen transport, to provide new insights into CBF regulation that would be inaccessible in a conventional experimental context. Our study implicates vasomotion of smooth muscle actin-covered vessels, rather than pericyte-covered capillaries, as the main mechanism for modulating tissue oxygenation. We also resolve seemingly paradoxical observations in the literature around reduced blood velocity in response to arteriolar constrictions and deduce the cause to be propagation of constrictions to upstream penetrating arterioles. We provide support for pericytes acting as signalling conduits for upstream smooth muscle activation, and erythrocyte deformation as a complementary regulatory mechanism. Finally, we caution against the use of blood velocity as a proxy measurement for flow. Our combined imaging-modelling platform complements conventional experimentation allowing cerebrovascular physiology to be probed in unprecedented detail.

scholarly journals Organizational Hierarchy and Structural Diversity of Microvascular Pericytes in Adult Mouse Cortex

2017 ◽  
Author(s):  
Roger I. Grant ◽  
David A. Hartmann ◽  
Robert G. Underly ◽  
Andrée-Anne Berthiaume ◽  
Narayan R. Bhat ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Actin ◽  
Muscle Cells ◽  
Cell Types ◽  
Mural Cell ◽  
Mural Cells ◽  
Mouse Cortex ◽  
Transitional Cells ◽  
Brain Microvasculature

ABSTRACTSmooth muscle cells and pericytes, together called mural cells, coordinate many distinct vascular functions. Smooth muscle cells are ring-shaped and cover arterioles with circumferential processes, whereas pericytes extend thin processes that run longitudinally along capillaries. In between these canonical mural cell types are cells with mixed phenotype of both smooth muscle cells and pericytes. Recent studies suggest that these transitional cells are critical for controlling blood flow to the capillary bed during health and disease, but there remains confusion on how to identify them and where they are located in the brain microvasculature. To address this issue, we measured the morphology, vascular territory, and α-smooth muscle actin content of structurally diverse mural cells in adult mouse cortex. We first imaged intact 3-D vascular networks to establish the locations of major gradations in mural cell appearance as arterioles branched into capillaries. We then imaged individual mural cells occupying the regions within these gradations. This revealed two transitional cells that were often similar in appearance, but with sharply contrasting levels of α-smooth muscle actin. Our findings highlight the diversity of mural cell morphologies in brain microvasculature, and provide guidance for identification and categorization of mural cell types.

scholarly journals Angiocrine FSTL1 insufficiency leads to atrial and vein wall fibrosis via SMAD3 activation

2019 ◽  
Author(s):  
Haijuan Jiang ◽  
Luqing Zhang ◽  
Xuelian Liu ◽  
Wei Sun ◽  
Katsuhiro Kato ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Heart Valves ◽  
Smooth Muscle Actin ◽  
Vascular Wall ◽  
Cell Interaction ◽  
Alpha Smooth Muscle Actin ◽  
Vein Wall ◽  
Mural Cell ◽  
Smad3 Phosphorylation ◽  
Cardiovascular Fibrosis

AbstractAngiocrine factors, mediating the endothelial-mural cell interaction in vascular wall construction as well as maintenance, are incompletely characterized. Here we show that loss of follistatin-like protein 1 (FSTL1) in endothelial cells (Fstl1ECKO) led to an increase of pulmonary vascular resistance, resulting in the heart regurgitation especially with tricuspid valves. However, this abnormality was not detected in mutant mice with Fstl1 deletion in smooth muscle cells or hematopoietic cells. We further showed that there was excessive alpha-smooth muscle actin (αSMA) associated with atrial endocardia, heart valves, veins and microvessels after the endothelial FSTL1 deletion. Consistently, there was an increase of collagen deposition as demonstrated in livers of Fstl1ECKO mutants. The SMAD3 phosphorylation was significantly enhanced and pSMAD3 staining was colocalized with αSMA in vein walls, suggesting the activation of TGFβ signaling in vascular mural cells of Fstl1ECKO mice. The findings imply that endothelial FSTL1 is critical for the homeostasis of atria and veins and its insufficiency may favor cardiovascular fibrosis leading to heart failure.

Abstract 724: Synectin is Required for Normal PDGF Secretion and Smooth Muscle Cell Basic Science Recruitment

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Julie M Paye ◽  
Thomas W Chittenden ◽  
Li-Kun Phng ◽  
Holger Gerhardt ◽  
Michael Simons
Keyword(s):  
Endothelial Cells ◽  
Transcriptional Regulation ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Smooth Muscle Actin ◽  
Alpha Smooth Muscle Actin ◽  
Arterial Tree ◽  
Mural Cell ◽  
Post Transcriptional Regulation

Background: Synectin, a ubiquitously expressed scaffold and PDZ protein, has been shown to be a key regulator in the formation of arterial vasculature. Primary arterial endothelial cells isolated from synectin−/− mice exhibited defects in PDGF signaling that were not present in arterial synectin+/+ or either venous synectin+/+ or synectin−/− endothelial cells. Methods: To address the role of synectin in mural cell recruitment, retinas from synectin−/− (KO) and synectin+/+ (WT) mice were stained for isolectin and alpha-smooth muscle actin. To determine the mechanisms responsible for defective smooth muscle cells recruitment, primary arterial and venous endothelial (EC) and smooth muscle (SMC) cells were isolated from synectin+/+ and synectin−/− mice. Results: Examination of the retinal vasculature in synectin−/− mice demonstrated poor smooth muscle cell coverage of the forming arterial tree with a number of SMC cells sitting some distance away from the vessels, a defect reminiscent of retinal abnormalities observed in PDGF-B−/− mice. Western blot analysis of lysates from primary KO SMC demonstrated levels of PDGFR-β analogous to WT, although expression of PDGF-B was markedly reduced in lysates from arterial, but not venous, primary KO endothelial cells. Transduction of KO EC with an adenoviral synectin construct was sufficient to restore PDGF-B protein levels. Further, qPCR was used to determine whether defects in PDGF-B protein production were at the transcription or translation level. Interestingly, there was only a minor decrease in the amount of PDGF-B mRNA in KO compared to WT EC, suggesting that synectin deficiency has selectively affected post-transcriptional regulation of PDGF-B expression. Migration of WT and KO SMC in response to PDGF-B or conditioned media from WT and KO endothelial cells was also assessed to determine the cell type specificity of PDGF defects in KO mice. Conclusions: Synectin is required for post-transcriptional regulation of PDGF-B in endothelial cells. Deficits in PDGF-B secretion by synectin−/− endothelial cells result in inadequate smooth muscle recruitment and coverage of arterial vessels.

scholarly journals Organizational hierarchy and structural diversity of microvascular pericytes in adult mouse cortex

2017 ◽  
Vol 39 (3) ◽  
pp. 411-425 ◽  
Author(s):  
Roger I Grant ◽  
David A Hartmann ◽  
Robert G Underly ◽  
Andrée-Anne Berthiaume ◽  
Narayan R Bhat ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Actin ◽  
Muscle Cells ◽  
Cell Types ◽  
Mural Cell ◽  
Mural Cells ◽  
Mouse Cortex ◽  
Transitional Cells ◽  
Brain Microvasculature

Smooth muscle cells and pericytes, together called mural cells, coordinate many distinct vascular functions. Canonically, smooth muscle cells are ring-shaped and cover arterioles with circumferential processes, whereas pericytes extend thin processes that run longitudinally along capillaries. In between these canonical mural cell types are cells with features of both smooth muscle cells and pericytes. Recent studies suggest that these transitional cells are critical for controlling blood flow to the capillary bed during health and disease, but there remains confusion on how to identify them and where they are located in the brain microvasculature. To address this issue, we measured the morphology, vascular territory, and α-smooth muscle actin content of structurally diverse mural cells in adult mouse cortex. We first imaged intact 3D vascular networks to establish the locations of major gradations in mural cell appearance as arterioles branched into capillaries. We then imaged individual mural cells occupying the regions within these gradations. This revealed two transitional cells that were often similar in appearance, but with sharply contrasting levels of α-smooth muscle actin. Our findings highlight the diversity of mural cell morphologies in brain microvasculature, and provide guidance for identification and categorization of mural cell types.

scholarly journals Immunoreactivity and a new staining method of monocarboxylate transporter 1 located in endothelial cells of cerebral vessels of human brain in distinguishing cerebral venules from arterioles

2021 ◽  
Vol 65 (s1) ◽  
Author(s):  
Yuan Cao ◽  
Dong-Hui Ao ◽  
Chao Ma ◽  
Wen-Ying Qiu ◽  
Yi-Cheng Zhu
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Human Brain ◽  
Smooth Muscle Actin ◽  
Cerebral Vessels ◽  
Monocarboxylate Transporter ◽  
Specific Marker ◽  
Cerebral Veins ◽  
Internal Elastic Lamina ◽  
Monocarboxylate Transporter 1

Distinguishing brain venules from arterioles with arteriolosclerosis is less reliable using traditional staining methods. We aimed to immunohistochemically assess the monocarboxylate transporter 1 (MCT1), a specific marker of venous endothelium found in rodent studies, in different caliber vessels in human brains. Both largeand small-caliber cerebral vessels were dissected from four autopsy donors. Immunoreactivity for MCT1 was examined in all autopsied human brain tissues, and then each vessel was identified by neuropathologists using hematoxylin and eosin stain, the Verhoeff’s Van Gieson stain, immunohistochemical stain with antibodies for α-smooth muscle actin and MCT1 in sequence. A total of 61 cerebral vessels, including 29 arteries and 32 veins were assessed. Immunoreactivity for MCT1 was observed in the endothelial cells of various caliber veins as well as the capillaries, whereas that was immunenegative in the endothelium of arteries. The different labeling patterns for MCT1 could aid in distinguishing various caliber veins from arteries, whereas assessment using the vessel shape, the internal elastic lamina, and the pattern of smooth muscle fibers failed to make the distinction between small-caliber veins and sclerotic arterioles. In conclusion, MCT1 immunohistochemical staining is a sensitive and reliable method to distinguish cerebral veins from arteries.

scholarly journals 20-HETE-promoted cerebral blow flow autoregulation is associated with enhanced α-smooth muscle actin positive cerebrovascular pericyte contractility

2021 ◽  
Author(s):  
Yedan Liu ◽  
Huawei Zhang ◽  
Tina Yu ◽  
Xing Fang ◽  
Jane J. Ryu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Essential Role ◽  
Smooth Muscle Actin ◽  
Dienoic Acid ◽  
Muscle Actin ◽  
Alpha Smooth Muscle Actin ◽  
Synthesis Inhibitor ◽  
Mural Cell ◽  
Cell Contractility ◽  
Sd Rats

ABSTRACTWe previously reported that deficiency in 20-HETE or CYP4A impaired the myogenic response and autoregulation of cerebral blood flow (CBF) in rats. The present study demonstrated that CYP4A was coexpressed with alpha-smooth muscle actin (α-SMA) in vascular smooth muscle cells (VSMCs) and most pericytes along parenchymal arteries (PAs) isolated from SD rats. Cell contractile capabilities of cerebral VSMCs and pericytes were reduced with a 20-HETE synthesis inhibitor, N-Hydroxy-N′-(4-butyl-2-methylphenyl)-formamidine (HET0016) but restored with 20-HETE analog 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid (WIT003). Similarly, intact myogenic responses of the middle cerebral artery and PA of SD rats decreased with HET0016 and rescued by WIT003. Lastly, HET0016 impaired well autoregulated CBF in the surface and deep cortex of SD rats. These results demonstrate that 20-HETE has a direct effect on cerebral mural cell contractility that may play an essential role in CBF autoregulation.

Sign in / Sign up

Export Citation Format

Share Document