Endothelin-1 Gene Suppression by Shear Stress: Pharmacological Evaluation of the Role of Tyrosine Kinase, Intracellular Calcium, Cytoskeleton, and Mechanosensitive Channels

Malek, Adel M.; Zhang, Janet; Jiang, Jianwei; Alper, Seth L.; Izumo, Seigo

doi:10.1006/jmcc.1998.0873

Cited by 67 publications

(39 citation statements)

References 23 publications

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“…During normal cardiac development, cardiac performance increases (Clark and Hu, 1982;Clark et al, 1986) and results in gradual changes in shear stress that either up-or downregulate the expression of shear-stress-responsive genes (Malek et al, 1999;Topper and Gimbrone, 1999). In vitro studies have demonstrated that endothelial cells are subjected to fluid shear stress as a result of blood flow and are aligned in the direction of the flow (Malek and Izumo, 1996;Malek et al, 1999) and that changes in shear stress especially cause alterations in gene expression (Fisher et al, 2001). Shear stress depends directly on volume flow (Goldsmith and Turitto, 1986).…”

Section: Discussionmentioning

confidence: 99%

Acutely altered hemodynamics following venous obstruction in the early chick embryo

Vos

Ursem

Hop

et al. 2003

Journal of Experimental Biology

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SUMMARYIn the venous clip model specific cardiac malformations are induced in the chick embryo by obstructing the right lateral vitelline vein with a microclip. Clipping alters venous return and intracardiac laminar blood flow patterns,with secondary effects on the mechanical load of the embryonic myocardium. We investigated the instantaneous effects of clipping the right lateral vitelline vein on hemodynamics in the stage-17 chick embryo. 32 chick embryos HH 17 were subdivided into venous clipped (N=16) and matched control embryos(N=16). Dorsal aortic blood flow velocity was measured with a 20 MHz pulsed Doppler meter. A time series of eight successive measurements per embryo was made starting just before clipping and ending 5h after clipping. Heart rate, peak systolic velocity, time-averaged velocity, peak blood flow,mean blood flow, peak acceleration and stroke volume were determined. All hemodynamic parameters decreased acutely after venous clipping and only three out of seven parameters (heart rate, time-averaged velocity and mean blood flow) showed a recovery to baseline values during the 5h study period. We conclude that the experimental alteration of venous return has major acute effects on hemodynamics in the chick embryo. These effects may be responsible for the observed cardiac malformations after clipping.

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Section: Discussionmentioning

confidence: 99%

Acutely altered hemodynamics following venous obstruction in the early chick embryo

Vos

Ursem

Hop

et al. 2003

Journal of Experimental Biology

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“…ET-1 mRNA levels are upregulated by hypocapnia and downregulated by hypoxia [31]. In endothelial cells, ET-1 mRNA initially increases then decreases by mechanical shear stress and stretch [32], but is consistently decreased in response to NO, prostacyclin and atrial natriuretic factor [9,33,34].…”

Section: Et Synthesismentioning

confidence: 99%

The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

Hynynen

Khalil²

2006

PRC

107

105

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The discovery of endothelin two decades ago has now evolved into an intricate vascular endothelin (ET) system. Several ET isoforms, receptors, signaling pathways, agonists, antagonists, and clinical applications have been identified and documented in first-rate patents. The role of ET as one of the most potent endothelium-derived vasoconstricting factors is now complemented by a newly discovered role in vascular relaxation. ET synthesis is initiated by the transcription of ET genes in endothelial cells and the generation of the gene products preproET and big ET, which are further cleaved by specific ET converting enzymes into ET-1, -2, -3 and -4 isoforms. ET isoforms bind with different affinities to ET A and ET B2 receptors in vascular smooth muscle, and stimulate [Ca 2+ ] i , protein kinase C, mitogen-activated protein kinase and other signaling mechanisms of smooth muscle contraction, growth and proliferation. ET also binds to endothelial ET B1 receptors, which mediate the release of vasodilator substances such as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor. Endothelial ET B1 receptors may also function in ET re-uptake and clearance. Although the effects of ET on vascular function and growth are well-recognized, the role of ET and its receptors in the regulation of blood pressure and in the pathogenesis of hypertension is not clearly established. Salt-dependent hypertension in experimental animals and some forms of moderate to severe hypertension in human may show elevated levels of plasma or vascular ET; however, other forms of hypertension show normal ET levels. The currently available ET receptor antagonists reduce blood pressure in some forms of experimental hypertension. Careful examination of recent patents may identify more effective and specific modulators of the vascular ET system for clinical use in human hypertension.

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“…Shear stress induces rapid and significant downregulation of ET-1 mRNA expression and peptide release with respect to static conditions in bovine aortic endothelial cells and human umbilical vein endothelial cells. 24,25 ET-1 plays an important role in hypertension. Besides its blood pressure raising effect in human beings, ET-1 induces vascular and myocardial hypertrophies, which are independent risk factors for cardiovascular morbidity and mortality.…”

mentioning

confidence: 99%

A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

Zhang

Wang

Feng

et al. 2016

IJN

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Endothelin-1 Gene Suppression by Shear Stress: Pharmacological Evaluation of the Role of Tyrosine Kinase, Intracellular Calcium, Cytoskeleton, and Mechanosensitive Channels

Cited by 67 publications

References 23 publications

Acutely altered hemodynamics following venous obstruction in the early chick embryo

Acutely altered hemodynamics following venous obstruction in the early chick embryo

The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

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