Endothelin-1 Is a Selective Vasoconstrictor: Studies on Human, Dog and Rabbit Blood Vessels in vitro and in vivo

Abstract Objective Endothelin-1 plays an important role in the pathogenesis of severe pulmonary hypertension. The + 139 ‘A’, adenine insertion variant in 5′UTR of edn1 gene has been reported to be associated with increased expression of Endothelin-1 in vitro. The aim of present study was to explore the association of this variant with the circulating levels of Endothelin-1 in vivo using archived DNA and plasma samples from 38 paediatric congenital heart disease (cyanotic and acyanotic) patients with severe pulmonary hypertension. Results The plasma Endothelin-1 levels were highly varied ranging from 1.63 to75.16 pg/ml. The + 139 ‘A’ insertion variant in 5′UTR of edn1 was seen in 8 out of 38 cases with only one acyanotic sample demonstrating homozygosity of inserted ‘A’ allele at + 139 site (4A/4A genotype). The plasma Endothelin-1 levels in children with homozygous variant 3A/3A genotype were comparable in cyanotic and acyanotic groups. Lone 4A/4A acyanotic sample had ET-1 levels similar to the median value of ET-1 associated with 3A/3A genotype and was absent in cyanotic group presumably due to deleterious higher ET-1 levels. The discussed observations, limited by the small sample size, are suggestive of homozygous adenine insertion variant posing a risk in cyanotic babies with Severe Pulmonary Hypertension.

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EXTRAHEPATIC AND EXTRARENAL RENIN INACTIVATION IN THE DOG

Journal of Endocrinology ◽

10.1677/joe.0.0600217 ◽

1974 ◽

Vol 60 (2) ◽

pp. 217-222

Author(s):

R. FAGARD ◽

E. FOSSION ◽

M. CAMPFORTS ◽

A. AMERY

Keyword(s):

Blood Vessels ◽

Pulmonary Circulation ◽

Plasma Renin ◽

Glass Container ◽

Plasma Renin Concentration ◽

Vascular Beds ◽

Extrarenal Renin

SUMMARY It was demonstrated previously that renin disappears quickly from the circulation after nephrectomy in the hepatectomized dog. In the present study the plasma renin concentration (PRC) was measured in the efferent and afferent blood vessels of several vascular beds (pulmonary circulation, splanchnic region, spleen, both inferior limbs and pelvis, head) in the anhepatic and in the anhepatic and anephric dog in order to investigate extrarenal and extrahepatic renin inactivation. However, no significant arteriovenous differences in PRC could be traced. The blood of these dogs kept in vitro at 37 °C in a glass container showed no decline in PRC within 3 h of removal. Therefore no specific extrahepatic and extrarenal renin-inactivating mechanism was found which could explain the rapid disappearance of renin from the blood in vivo in the anhepatic and anephric dog.

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Recombinant TAT-Thymosin β-4 Promotes Angiogenesis by Activating VEGFR2 Signaling Pathway

10.21203/rs.3.rs-913761/v1 ◽

2021 ◽

Author(s):

Chul Min Kim ◽

Yun-Mi Jeong ◽

Jae-Hun Kim ◽

Guolong Jin ◽

Hyeongkwon Oh ◽

...

Keyword(s):

Blood Vessels ◽

Signaling Pathway ◽

Dynamic Equilibrium ◽

Common Type ◽

Cell Penetrating Peptide ◽

Angiogenic Potential ◽

Angiogenic Effect ◽

Vegfr2 Signaling

Abstract Thymosin β-4 is a 43-amino acid intracellular polypeptide that was originally isolated from bovine thymus. Of the 16 known thymosin families, thymosin β-4 is the most common type found in all tissues. Thymosin β-4 regulates angiogenesis, cell differentiation, morphogenesis, migration, and organogenesis and is linked to a dynamic equilibrium between G-actin and F-actin. In particular, thymosin β-4 is well-known for its angiogenic and anti-apoptotic functions. In this study, we synthesized thymosin β-4 linked with the well-known cell-penetrating peptide TAT (YGRKKRRRQRRR). TAT-thymosin β-4 promotes angiogenesis and cell migration in vitro via the VEGFR2 signaling pathway and reduces apoptosis. To examine angiogenic potential in vivo, a Matrigel Plus assay was conducted that revealed the angiogenic effect of TAT-thymosin β-4. In conclusion, TAT-thymosin β-4 promotes blood vessels and is expected to be applicable in regenerative medicine for all organs requiring blood vessels.

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Amylin: Localization, Effects on Cerebral Arteries and on Local Cerebral Blood Flow in the Cat

The Scientific World JOURNAL ◽

10.1100/tsw.2001.23 ◽

2001 ◽

Vol 1 ◽

pp. 168-180 ◽

Cited By ~ 33

Author(s):

Lars Edvinsson ◽

Peter J. Goadsby ◽

Rolf Uddman

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Blood Vessels ◽

Cerebral Arteries ◽

In Vivo Studies ◽

Cerebral Blood Vessels ◽

Local Cerebral Blood Flow ◽

Doppler Flowmetry

Amylin and adrenomedullin are two peptides structurally related to calcitonin gene-related peptide (CGRP). We studied the occurrence of amylin in trigeminal ganglia and cerebral blood vessels of the cat with immunocytochemistry and evaluated the role of amylin and adrenomedullin in the cerebral circulation by in vitro and in vivo pharmacology. Immunocytochemistry revealed that numerous nerve cell bodies in the trigeminal ganglion contained CGRP immunoreactivity (-ir); some of these also expressed amylin-ir but none adrenomedullin-ir. There were numerous nerve fibres surrounding cerebral blood vessels that contained CGRP-ir. Occasional fibres contained amylin-ir while we observed no adrenomedullin-ir in the vessel walls. With RT-PCR and Real-Time�PCR we revealed the presence of mRNA for calcitonin receptor-like receptor (CLRL) and receptor-activity-modifying proteins (RAMPs) in cat cerebral arteries. In vitro studies revealed that amylin, adrenomedullin, and CGRP relaxed ring segments of the cat middle cerebral artery. CGRP and amylin caused concentration-dependent relaxations at low concentrations of PGF2a-precontracted segment (with or without endothelium) whereas only at high concentration did adrenomedullin cause relaxation. CGRP8-37 blocked the CGRP and amylin induced relaxations in a parallel fashion. In vivo studies of amylin, adrenomedullin, and CGRP showed a brisk reproducible increase in local cerebral blood flow as examined using laser Doppler flowmetry applied to the cerebral cortex of the a-chloralose�anesthetized cat. The responses to amylin and CGRP were blocked by CGRP8-37. The studies suggest that there is a functional sub-set of amylin-containing trigeminal neurons which probably act via CGRP receptors.

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Scaffolds in tissue engineering of blood vessels

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y10-073 ◽

2010 ◽

Vol 88 (9) ◽

pp. 855-873 ◽

Cited By ~ 60

Author(s):

Divya Pankajakshan ◽

Devendra K. Agrawal

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Blood Vessels ◽

Vascular Tissue ◽

Small Diameter ◽

Biological Scaffolds ◽

Hemodynamic Forces ◽

Biodegradable Scaffolds

Tissue engineering of small diameter (<5 mm) blood vessels is a promising approach for developing viable alternatives to autologous vascular grafts. It involves in vitro seeding of cells onto a scaffold on which the cells attach, proliferate, and differentiate while secreting the components of extracellular matrix that are required for creating the tissue. The scaffold should provide the initial requisite mechanical strength to withstand in vivo hemodynamic forces until vascular smooth muscle cells and fibroblasts reinforce the extracellular matrix of the vessel wall. Hence, the choice of scaffold is crucial for providing guidance cues to the cells to behave in the required manner to produce tissues and organs of the desired shape and size. Several types of scaffolds have been used for the reconstruction of blood vessels. They can be broadly classified as biological scaffolds, decellularized matrices, and polymeric biodegradable scaffolds. This review focuses on the different types of scaffolds that have been designed, developed, and tested for tissue engineering of blood vessels, including use of stem cells in vascular tissue engineering.

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Effects of endothelin-1 on renal function and renin secretion in vivo and in vitro

European Journal of Pharmacology ◽

10.1016/0014-2999(90)92135-6 ◽

1990 ◽

Vol 183 (5) ◽

pp. 1814-1815

Author(s):

S. Morimoto ◽

K. Hisaki ◽

K. Nakase ◽

R. Ikegawa ◽

K. Hayashi ◽

...

Keyword(s):

Renal Function ◽

Renin Secretion ◽

Endothelin 1

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In vivo and in vitro study of osteogenic potency of endothelin-1 on bone marrow-derived mesenchymal stem cells

Experimental Cell Research ◽

10.1016/j.yexcr.2017.04.018 ◽

2017 ◽

Vol 357 (1) ◽

pp. 25-32 ◽

Cited By ~ 6

Author(s):

Long-Wei Hu ◽

Xiao Wang ◽

Xin-Qun Jiang ◽

Li-Qun Xu ◽

Hong-Ya Pan

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

In Vitro Study ◽

Vitro Study ◽

Endothelin 1

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Abstract 237: PRMT1-p53-Slug Axis Regulates Epicardial EMT and Ventricular Development

Circulation Research ◽

10.1161/res.121.suppl_1.237 ◽

2017 ◽

Vol 121 (suppl_1) ◽

Author(s):

Olan Jackson-Weaver ◽

Jian Wu ◽

Yongchao Gou ◽

Yibu Chen ◽

Meng Li ◽

...

Keyword(s):

Blood Vessels ◽

Heart Development ◽

Cultured Cells ◽

Migration And Invasion ◽

P53 Expression ◽

Epicardial Cells ◽

Coronary Blood Vessels

Rationale: Epicardial epithelial-to-mesenchymal trasition (EMT) is a vital process in embryonic heart development. During EMT, epicardial cells acquire migratory and invasive properties, and differentiate into new cell types, including cardiac fibroblasts and coronary smooth muscle cells. Non-histone protein methylation is an emerging modulator of cell signaling. We have recently established a role for protein arginine methyltransferase-1 (PRMT1) in TGF-β-induced EMT in cultured cells. Objective: To determine the role of PRMT1 in epicardial EMT. Methods and Results: We investigated the role of PRMT1 in epicardial EMT in mouse epicardial cells. Embryonic day 9.5 (E9.5) tamoxifen administration of WT1-Cre ERT ;PRMT1 fl/fl ;ROSA-YFP fl/fl mouse embryos was used to delete PRMT1 in the epicardium. Epicardial PRMT1 deletion led to reduced epicardial migration into the myocardium, a thinner compact myocardial layer, and dilated coronary blood vessels at E15.5. Using the epicardial cell line MEC1, we found that PRMT1 siRNA prevented the increase in mesenchymal proteins Slug and Fibronectin and the decrease in epithelial protein E-Cadherin during TGF-β treatment-induced EMT. PRMT1 siRNA also reduced the migration and invasion of MEC1 cells. We further identified that PRMT1 siRNA also increased the expression of p53, a key regulator of the Slug degradation pathway. PRMT1 siRNA increases p53 expression by decreasing p53 degradation, and shifted p53 localization to the cytoplasm. In vitro methylation assays further demonstrated that PRMT1 methylates p53. Knockdown of p53 increased Slug levels and enhanced EMT, establishing p53 as a regulator of epicardial EMT through controlling Slug expression. Furthermore, RNAseq experiments in MEC1 cells demonstrated that 40% (545/1,351) of TGF-β-induced transcriptional changes were prevented by PRMT1 siRNA. Furthermore, when p53 and PRMT1 were simultaneously knocked down, TGF-β induced transcriptional control of 37% (201/545) of these PRMT1-dependent genes was restored. Conclusions: The PRMT1-p53-Slug pathway is necessary for epicardial EMT in cultured MEC1 cells as well as in the epicardium in vivo . Epicardial PRMT1 is required for the development of compact myocardium and coronary blood vessels.

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Endothelial ERK1/2 signaling maintains integrity of the quiescent endothelium

Journal of Experimental Medicine ◽

10.1084/jem.20182151 ◽

2019 ◽

Vol 216 (8) ◽

pp. 1874-1890 ◽

Cited By ~ 13

Author(s):

Nicolas Ricard ◽

Rizaldy P. Scott ◽

Carmen J. Booth ◽

Heino Velazquez ◽

Nicholas A. Cilfone ◽

...

Keyword(s):

Rapid Onset ◽

Cardiac Conduction ◽

Tgfβ Signaling ◽

Mesenchymal Transition ◽

Endothelin 1 ◽

Endocrine Organs ◽

Endothelial To Mesenchymal Transition

To define the role of ERK1/2 signaling in the quiescent endothelium, we induced endothelial Erk2 knockout in adult Erk1−/− mice. This resulted in a rapid onset of hypertension, a decrease in eNOS expression, and an increase in endothelin-1 plasma levels, with all mice dying within 5 wk. Immunostaining and endothelial fate mapping showed a robust increase in TGFβ signaling leading to widespread endothelial-to-mesenchymal transition (EndMT). Fibrosis affecting the cardiac conduction system was responsible for the universal lethality in these mice. Other findings included renal endotheliosis, loss of fenestrated endothelia in endocrine organs, and hemorrhages. An ensemble computational intelligence strategy, comprising deep learning and probabilistic programing of RNA-seq data, causally linked the loss of ERK1/2 in HUVECs in vitro to activation of TGFβ signaling, EndMT, suppression of eNOS, and induction of endothelin-1 expression. All in silico predictions were verified in vitro and in vivo. In summary, these data establish the key role played by ERK1/2 signaling in the maintenance of vascular normalcy.

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