Endothelin ET<sub>A</sub> receptor expression in human cerebrovascular smooth muscle cells

Yu, Julie C.M.; Pickard, John D.; Davenport, Anthony P.

doi:10.1111/j.1476-5381.1995.tb15093.x

Cited by 37 publications

(18 citation statements)

References 46 publications

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“…ETs are synthesised predominantly by endothelial cells in blood vessels and released to the basolateral compartment, but proportions are also released into the vascular lumen [9]. Smooth muscle cells in culture [10] and other cells such as fibroblasts and mesangial cells can also produce endothelins under certain conditions [11,12].…”

Section: Ets and Et Receptors: Vasoconstiction Vs Tissue Remodellingmentioning

confidence: 99%

Connective Tissue Remodeling: Cross-Talk between Endothelins and Matrix Metalloproteinases

Abraham¹,

Ponticos²,

Nagase³

2005

CVP

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Connective tissue remodeling is achieved by a complex process involving several cell types, a plethora of growth factors, cytokines, chemokines and turnover of extracellular matrix (ECM). The main enzymes that degrade ECM molecules are matrix metalloproteinases (MMPs) and their activities are regulated by endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Recent studies have indicated that endothelins and their receptor expression affects tissue remodeling and repair. Endothelins are rapidly produced by endothelial cells in response to tissue injury and they have potent vasoconstrictive properties. They also promote tissue remodeling through activation of resident connective tissue cells and controlling the production of MMPs and TIMPs by the activated cells. In this review we present the cross-talk between the endothelins and the MMP-TIMP system and their implications in controlling the normal and abnormal tissue remodeling.

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Section: Ets and Et Receptors: Vasoconstiction Vs Tissue Remodellingmentioning

confidence: 99%

Connective Tissue Remodeling: Cross-Talk between Endothelins and Matrix Metalloproteinases

Abraham¹,

Ponticos²,

Nagase³

2005

CVP

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“…EDN1 is produced primarily by the vascular endothelium and smooth-muscle cells and is involved in maintaining vasomotor control and vascular homeostasis (10). EDNRA is found on vascular smooth-muscle cells, including the cerebrovasculature, along with the heart, kidney, and neuronal cells (12), and mediates the vasoconstriction and mitogenic effects of EDN1 (13,14). On the other hand, EDNRB reside on both smooth-muscle and endothelial cells, with downstream signaling through nitric oxide (15).…”

Section: −7mentioning

confidence: 99%

Common variant near the endothelin receptor type A ( EDNRA ) gene is associated with intracranial aneurysm risk

Yasuno

Bakırcıoğlu

Low

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

104

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The pathogenesis of intracranial aneurysm (IA) formation and rupture is complex, with significant contribution from genetic factors. We previously reported genome-wide association studies based on European discovery and Japanese replication cohorts of 5,891 cases and 14,181 controls that identified five disease-related loci. These studies were based on testing replication of genomic regions that contained SNPs with posterior probability of association (PPA) greater than 0.5 in the discovery cohort. To identify additional IA risk loci, we pursued 14 loci with PPAs in the discovery cohort between 0.1 and 0.5. Twenty-five SNPs from these loci were genotyped using two independent Japanese cohorts, and the results from discovery and replication cohorts were combined by metaanalysis. The results demonstrated significant association of IA with rs6841581 on chromosome 4q31.23, immediately 5′ of the endothelin receptor type A with P = 2.2 × 10 −8 [odds ratio (OR) = 1.22, PPA = 0.986]. We also observed substantially increased evidence of association for two other regions on chromosomes 12q22 (OR = 1.16, P = 1.1 × 10 −7, PPA = 0.934) and 20p12.1 (OR = 1.20, P = 6.9 × 10 −7, PPA = 0.728). Although endothelin signaling has been hypothesized to play a role in various cardiovascular disorders for over two decades, our results are unique in providing genetic evidence for a significant association with IA and suggest that manipulation of the endothelin pathway may have important implications for the prevention and treatment of IA.subarachnoid hemorrhage | stroke | genetic risk loci I ntracranial aneurysms (IAs) are balloon-like dilations of cerebral arteries and affect 2-5% of the population (1). Although most of these lesions are clinically silent, their rupture and consequent subarachnoid hemorrhage usually occurs between ages 40 and 60 without prior warning, resulting in substantial morbidity and mortality (2, 3).Aside from the well-established risk factors, such as hypertension, smoking, female sex (4), and high shear stress imposed on the cerebrovasculature (5), there is evidence for significant genetic contribution to IA pathogenesis (6). As is the case for other multifactorial diseases, both common and rare variants are thought to contribute to IA. In an attempt to identify common variants that confer risk of IA, we previously completed two genome-wide association studies of IA (6, 7). The larger, second genome-wide association study (7) implemented a discovery and a replication phase using samples of European and Japanese descent, respectively. Using a discovery cohort of 2,780 cases and 12,515 controls, we analyzed 831,532 genotyped and imputed autosomal SNPs for association with IA. We used a Bayesian measure of the strength of association-the posterior probability of association (PPA)-to prioritize SNPs by calculating to what extent the data supports association with IA (7). This analysis revealed five loci with PPA > 0.5. Following replication genotyping using two independent Japanese cohorts and combining the discov...

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“…Interestingly, normal human cerebral arteries express mainly ETA whilst in vessel sample from patients with cerebral disease and neoplasms, ET B were mainly expressed suggesting a vascular involvement of this later receptor in pathological cerebrovascular diseases. In medial smooth muscle cells of human cerebral vessels, the expression of ET A and ET B was detected by RT-PCR and by autoradiographic binding studies [188].…”

Section: Distribution Of Endothelins In the Brain Endothelial Cellsmentioning

confidence: 99%

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

Schinelli¹

2006

CMC

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The endothelin system, consisting of three peptides, two peptidases and two G-protein coupled receptors, is widely expressed in the brain cell types and brain-derived tumor cell lines. The stimulation of endothelin receptors elicits a variety of short- and long-term changes at cellular level but the effects of the pharmacological modulation of the endothelin system in brain physiology and pathophysiology are, at the present time, poorly understood. Altered expression of endothelins (ETs) in reactive astrocytes has been observed in many pathological conditions of the human brain, such as infarcts, lacunae, traumatic conditions, Alzheimer's disease and inflammatory diseases of the brain. In addition, recent studies have shown that endothelin antagonists might inhibit growth and induce cell death in human melanoma cells in vitro and in vivo, and have emphasized a possible role of endothelin peptides as autocrine or paracrine factor in the proliferation and dissemination of tumor cell lines. Given the fact that brain cell and a variety of brain tumor cell lines express functional endothelin receptors, further studies are warranted to demonstrate a possible therapeutic role of endothelin agonists and antagonist in the pharmacological treatment of brain-related diseases and brain tumors.

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Endothelin ET_A receptor expression in human cerebrovascular smooth muscle cells

Abstract: 1 Endothelin (ET) has been implicated in cerebrovasospasm for example, following subarachnoid haemorrhage, and blocking the interaction of ET with its receptors on cerebral vessels, may be of therapeutic benefit. The aim of our study was

Cited by 37 publications

References 46 publications

Connective Tissue Remodeling: Cross-Talk between Endothelins and Matrix Metalloproteinases

Connective Tissue Remodeling: Cross-Talk between Endothelins and Matrix Metalloproteinases

Common variant near the endothelin receptor type A ( EDNRA ) gene is associated with intracranial aneurysm risk

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

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Endothelin ETA receptor expression in human cerebrovascular smooth muscle cells

Abstract: 1 Endothelin (ET) has been implicated in cerebrovasospasm for example, following subarachnoid haemorrhage, and blocking the interaction of ET with its receptors on cerebral vessels, may be of therapeutic benefit. The aim of our study was

Cited by 37 publications

References 46 publications

Connective Tissue Remodeling: Cross-Talk between Endothelins and Matrix Metalloproteinases

Connective Tissue Remodeling: Cross-Talk between Endothelins and Matrix Metalloproteinases

Common variant near the endothelin receptor type A ( EDNRA ) gene is associated with intracranial aneurysm risk

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

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Product

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Endothelin ET_A receptor expression in human cerebrovascular smooth muscle cells