Physiological fluid shear stress causes downregulation of endothelin-1 mRNA in bovine aortic endothelium

Malek, Adel M.; Izumo, Seigo

doi:10.1152/ajpcell.1992.263.2.c389

Cited by 274 publications

(154 citation statements)

References 27 publications

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“…10 ET is regulated in an autocrine fashion by physiochemical factors such as blood flow, pulsatile stretch, sheer stress, and pH. [11][12][13] Acute hypoxia leads to selective stimulation of the ET-1 gene and ET synthesis in the pulmonary vasculature. 14 ET-1 biosynthesis is also stimulated by low-density lipoprotein cholesterol and glucose, and thrombin.…”

mentioning

confidence: 99%

Endothelin Receptor Blockers in Cardiovascular Disease

Rich¹,

McLaughlin²

2003

Circulation

197

125

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Abstract-The endothelin (ET) system is comprised of 4 active ETs, with ET-1 being the predominant isoform in the cardiovascular system. Because of the potent vasoconstricting and mitogenic effects of ET-1 and its involvement in various cardiovascular diseases, blockade of the ET receptor has received considerable attention. ET receptor antagonism has been demonstrated to be beneficial in patients with pulmonary hypertension. The nonselective ET receptor antagonist bosentan improves exercise capacity and increases time to clinical worsening in patients with pulmonary arterial hypertension. Key Words: endothelin Ⅲ heart failure Ⅲ pulmonary heart disease T he endothelin (ET) system, like other vascular regulatory systems, consists of a parent peptide that undergoes enzymatic activation and exerts its biologic effects by modulating specific receptors. Of the 4 active ETs (ET 1 through 4), ET-1 is the predominant isoform in the cardiovascular system, which is generated through the cleavage of prepro ET-1 to big ET-1 and then to ET-1 by the action of ET-converting enzymes. ET-1 is found in endothelial cells and is released toward the vascular smooth muscle consistent with a paracrine role, but it is also produced by smooth muscle cells and cardiomyocytes. 1,2 ET-1 has vasoconstrictive and mitogenic effects, stimulates the production of growth factors such as vascular endothelial growth factor and basic fibroblast growth factor, and potentiates the effects of transforming growth factor-␤ and platelet-derived growth factor. 3-7 Chronic ET-1 stimulation can result in myocardial fibrosis and hypertrophy and vascular fibrosis with extracellular matrix proliferation. 8 In the lung, ET-1 is abundantly expressed in the pulmonary vasculature and appears to play an important role in the regulation of pulmonary vascular tone. 9 ET-1 is also produced in leukocytes where it influences the production of a wide range of cytokines in the inflammatory response. 10 ET is regulated in an autocrine fashion by physiochemical factors such as blood flow, pulsatile stretch, sheer stress, and pH. 11-13 Acute hypoxia leads to selective stimulation of the ET-1 gene and ET synthesis in the pulmonary vasculature. 14 ET-1 biosynthesis is also stimulated by low-density lipoprotein cholesterol and glucose, and thrombin. 15,16 Endogenous inhibitors of ET-1 synthesis include nitric oxide, prostacyclin, atrial natriuretic peptides, and estrogens. [17][18][19][20] ET-1 exerts its major vascular effects through activation of 2 distinct G protein coupled ET A and ET B receptors. ET A receptors are found in the medial smooth muscle layers of the blood vessels, and atrial and ventricular myocardium. 21 When stimulated, the ET A receptors induce vasoconstriction and cellular proliferation by increasing intracellular calcium.ET B receptors are localized on endothelial cells and, to some extent, smooth muscle cells and macrophages. 22 The activation of ET B receptors stimulates the release of nitric oxide and prostacyclin and prevents apoptosis. 23 Normally, t...

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mentioning

confidence: 99%

Endothelin Receptor Blockers in Cardiovascular Disease

Rich¹,

McLaughlin²

2003

Circulation

197

125

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“…However, the mechanisms of regulation of mRNA expression by other substances remain to be elucidated. Although no SSRE (shear stress responsive element) was detected in the endothelin-1 gene, mRNA expression and endothelin production in endothelial cells are regulated by fluid shear stress: high shear stress (25 dynes/cm2) sharply decreases mRNA levels (20,21), whereas low shear stress (5 dynes /cm2) increases endothelin-1 mRNA expression (22). Pulsatile stretch also causes enhanced production of endothelin-1 in endothelial cells (23).…”

Section: -1 Endothelin Gene and Regulation Of Its Expressionmentioning

confidence: 99%

“…After more than six years, the cloning and characterization of ECE have finally been successfully achieved. ECE is considered to be a potential target for selectively interrupting the biosynthesis of endothelin; although this approach has proven to be extremely difficult, an N-and C-terminaltruncated analogue of big endothelin-1 , [Phe22] big endothelin-1 [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37], was recently shown to be a potent inhibitor of ECE-1, being at least 30-fold more potent that phosphoramidon in blocking big endothelin-linduced vasoconstriction in the kidney (38).…”

Section: -1 Endothelin Gene and Regulation Of Its Expressionmentioning

confidence: 99%

Molecular Pharmacology and Pathophysiological Significance of Endothelin

Goto

Hama

Kasuya

1996

Japanese Journal of Pharmacology

158

108

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ABSTRACT-Since the discovery of the most potent vasoconstrictor peptide, endothelin, in 1988, explosive investigations have rapidly clarified much of the basic pharmacological, biochemical and molecular biological features of endothelin, including the presence and structure of isopeptides and their genes (endothelin-1, -2 and -3), regulation of gene expression, intracellular processing, specific endothelia converting enzyme (ECE), receptor subtypes (ETA and ETB), intracellular signal transduction following receptor activation, etc. ECE was recently cloned, and its structure was shown to be a single transmembrane protein with a short intracellular N-terminal and a long extracellular C-terminal that contains the catalytic domain and numerous N-glycosylation sites. In addition to acute contractile or secretory actions, endothelin has been shown to exert long-term proliferative actions on many cell types. In this case, intracellular signal transduction appears to converge to activation of mitogen-activated protein kinase. As a recent dramatic advance, a number of non-peptide and orally active receptor antagonists have been developed. They, as well as current peptide antagonists, markedly accelerated the pace of investigations into the true pathophysiological roles of endogenous endothelin-1 in mature animals; e.g., hypertension, pulmonary hypertension, acute renal failure, cerebral vasospasm, vascular thickening, cardiac hypertrophy, chronic heart failure, etc. Thus, the interference with the endothelin pathway by either ECE-inhibition or receptor blockade may

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“…Ideally, ECs elongate and align with flow, integrin distribution is reorganized, improving EC adhesion, and antithrombic and vasoactive agents (nitric oxide (NO), endothelium-derived hyperpolarizing factor, prostacyclin and endothelin) are produced (16,17) to act on the vascular smooth muscle cells, which regulate the diameter of the vessel and so control local blood flow rate (18). Local regulation of vessel diameter helps to maintain WSS within the normal range.…”

Section: Introductionmentioning

confidence: 99%

Multi-scale interaction of particulate flow and the artery wall

Halliday

Atherton

Care

et al. 2011

Medical Engineering & Physics

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We discuss, from the perspective of basic science, the physical and biological processes which underlie atherosclerotic (plaque) initiation at the vascular endothelium, identifying the widely separated spatial and temporal scales which participate. We draw on current, related models of vessel wall evolution, paying particular attention to the role of particulate flow (blood is not a -2 -continuum fluid), and proceed to propose, then validate all the key components in a multiplycoupled, multi-scale modeling strategy (in qualitative terms only, note). Eventually, this strategy should lead to a quantitative, patient-specific understanding of the coupling between particulate flow and the endothelial state.

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Physiological fluid shear stress causes downregulation of endothelin-1 mRNA in bovine aortic endothelium

Cited by 274 publications

References 27 publications

Endothelin Receptor Blockers in Cardiovascular Disease

Endothelin Receptor Blockers in Cardiovascular Disease

Molecular Pharmacology and Pathophysiological Significance of Endothelin

Multi-scale interaction of particulate flow and the artery wall

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