Receptor Mechanism of Thrombin-Induced Endothelium-Dependent and Endothelium-Independent Coronary Vascular Effects in Dogs

Ku, David D.; Zaleski, Joanne K.

doi:10.1097/00005344-199310000-00015

Cited by 62 publications

(54 citation statements)

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“…56 In normal guinea-pig aortas, rabbit aortas and canine coronary arteries, thrombin has been reported to directly contract smooth muscle. 50,54,55,58 However, it has also been shown to have no direct contractile effect in normal rabbit mesenteric arteries, rabbit femoral arteries, or rat aortas, while causing slight contractions in normal rabbit basilar arteries, at high concentrations (unpublished observations). As a result, the endothelial cells are considered to be the primary cells mediating the vascular (Figure).…”

Section: The Role Of Pars In Vascular Physiologymentioning

confidence: 93%

The Roles of Proteinase-Activated Receptors in the Vascular Physiology and Pathophysiology

Hirano

2007

ATVB

136

121

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Abstract-Proteinase-activated receptors (PARs) belong to a family of G protein-coupled receptors, thus mediating the cellular effects of proteinases. In the vascular system, thrombin and other proteinases in the coagulation-fibrinolysis system are considered to be the physiologically relevant agonists, whereas PARs are among the most important mechanisms mediating the interaction between the coagulation-fibrinolysis system and the vascular wall. Under physiological conditions, PARs are mainly expressed in endothelial cells, and participate in the regulation of vascular tone, mostly by inducing endothelium-dependent relaxation. PARs in endothelial cells are also suggested to contribute to a proinflammatory phenotypic conversion and an increase in the permeability of vascular lesions. In smooth muscle cells, PARs mediate contraction, migration, proliferation, hypertrophy, and production of the extracellular matrix, thereby contributing to the development of vascular lesions and the pathophysiology of such vascular diseases as atherosclerosis. However, the expression of PARs in the smooth muscle of normal arteries is limited. The upregulation of PARs in the smooth muscle is thus considered to be a key step for PARs to participate in the pathogenesis of vascular lesions. Elucidating the molecular mechanism regulating the PARs expression is therefore important to develop new strategies for the prevention and treatment of vascular diseases. (Arterioscler Thromb Vasc Biol. 2007;27:27-36.)

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Section: The Role Of Pars In Vascular Physiologymentioning

confidence: 93%

The Roles of Proteinase-Activated Receptors in the Vascular Physiology and Pathophysiology

Hirano

2007

ATVB

136

121

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“…Thrombin was reported to induce endothelium-dependent relaxation (79,80,(98)(99)(100)(101), endothelium-dependent contraction (82) and endothelium-independent direct contraction in smooth muscle (79,80), depending on the species and type of blood vessel. The PAR-2-mediated regulation of vascular tone also varies with species and type of blood vessel, as observed with PAR-1.…”

Section: Endothelium-dependent Regulation Of Vascular Tone By Thrombimentioning

confidence: 99%

“…Prostaglandin H2 and thromboxane A2 were shown to contribute to the endothelium-dependent contraction (82). On the other hand, thrombin induces endothelium-independent contraction in guinea-pig aorta, rabbit aorta and canine coronary artery (79,80,98,108). In isolated human coronary rings, PAR-1-mediated endothelium-dependent relaxation dominated when the degree of intimal proliferation was minimal (79).…”

Section: Endothelium-dependent Regulation Of Vascular Tone By Thrombimentioning

confidence: 99%

Role of Protease-activated Receptors in the Vascular System

Hirano

Kobayashi

2003

JAT

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“…14,15 Receptor activation results in cell signaling and a number of different cellular functions. Within the vasculature, PAR-1 activation causes alteration of vascular tone 16 -18 ; stimulation of vascular smooth muscle proliferation 19 ; stimulation of vascular smooth muscle procollagen synthesis 20 ; activation of endo-thelial cells leading to release of nitric oxide, 18 endothelin, 21 prostaglandins, 22 and von Willebrand factor 23 ; alteration of adhesion molecule expression 24 ; and increased vascular permeability. 25,26 Several of these cellular functions, particularly stimulation of vascular smooth muscle proliferation and collagen synthesis, are integral to vascular wound healing.…”

mentioning

confidence: 99%

Altered Vascular Injury Responses in Mice Deficient in Protease-Activated Receptor-1

Cheung

D’Andrea

Andrade‐Gordon

et al. 1999

ATVB

115

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Abstract-Expression of protease-activated receptor-1 (PAR-1), a cell-surface receptor for thrombin, is increased in balloon-injured rat carotid artery and human atherosclerotic tissue. To examine the role of PAR-1 in vascular injury, we compared vascular injury responses in wild-type (WT) and PAR-1-deficient (PAR-1 Ϫ/Ϫ ) mice. Arterial injury was induced by inserting a flexible guidewire into the common carotid artery and withdrawing it 6 times with rotation. Bromodeoxyuridine, delivered subcutaneously by osmotic minipump, was used to measure cellular proliferation. Mice were perfusion-fixed at 1, 2, 5, 10, and 14 days after injury. Extensive endothelial damage, mural thrombosis, platelet adherence, and medial smooth muscle cell loss and necrosis were apparent at day 1 in both WT and PAR-1 Ϫ/Ϫ mice. The incidence of thrombosis or platelet deposition in WT and PAR-1 Ϫ/Ϫ mice declined from 100% at day 1 to 25% and 21%, respectively, at 14 days. Endothelial disruption, as assessed by Evan's blue uptake, was maximum at day 1 and declined by day 14. This apparent endothelial regrowth was similar in WT and PAR-1 Ϫ/Ϫ mice. Significant medial thickening at 14 days after injury was similar in WT (from 22.8Ϯ1.7 to 30.7Ϯ1.9 m) and PAR-1 Ϫ/Ϫ (from 23.2Ϯ2.1 to 30.5Ϯ2.2 m) mice. Medial area also increased in response to injury but to a lesser extent in PAR-1 Ϫ/Ϫ mice (from 0.0250Ϯ0.0044 to 0.0312Ϯ0.0047 mm 2 ) than in WT mice (from 0.0266Ϯ0.0040 to 0.0398Ϯ0.0050 mm 2 ). Neointima was variable and occurred in 6 of 13 WT and 5 of 12 PAR-1 Ϫ/Ϫ mice. However, intimal area tended to be less in PAR-1 Ϫ/Ϫ mice (0.0016Ϯ0.0007 mm 2 ) compared with WT mice (0.0082Ϯ0.0032 mm 2 ), although this difference did not achieve statistical significance (Pϭ0.06). Cell density was significantly greater in normal carotids from PAR-1 Ϫ/Ϫ (6.4Ϯ0.5ϫ10 3 /mm 2 ) compared with WT (4.3Ϯ0.8ϫ10 3 /mm 2 ) mice and remained elevated after injury. Vessel and lumen diameters tended to increase in WT mice after injury, whereas vessel diameter was unchanged and lumen diameter actually decreased in PAR-1 Ϫ/Ϫ mice. Cell proliferation in injured carotid arteries was similar in PAR-1 Ϫ/Ϫ and WT mice. Key Words: protease-activated receptor Ⅲ knockout mouse Ⅲ thrombin Ⅲ thrombin receptor Ⅲ cell proliferation S everal lines of evidence suggest a significant role for thrombin in vascular injury responses associated with thrombosis, atherosclerosis, and mechanical arterial injury, such as that caused by balloon angioplasty or stent implantation. [1][2][3] Concentrations of thrombin at sites of vascular injury are significantly elevated. For example, 5 hours after balloon injury of the rabbit aorta, thrombin activity was 50 fmol ⅐ min Ϫ1 ⅐ cm Ϫ2 , gradually decreasing to 10 fmol ⅐ min Ϫ1 ⅐ cm Ϫ2 at 24 hours after injury. 4 These levels were sustained for at least 10 days. In human plasma, thrombin concentrations in the vicinity of a thrombus have been estimated to be as high as 140 nmol/L. 5 In addition to evidence for elevated thrombin levels at sites of vascular injury...

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Receptor Mechanism of Thrombin-Induced Endothelium-Dependent and Endothelium-Independent Coronary Vascular Effects in Dogs

Cited by 62 publications

References 0 publications

The Roles of Proteinase-Activated Receptors in the Vascular Physiology and Pathophysiology

The Roles of Proteinase-Activated Receptors in the Vascular Physiology and Pathophysiology

Role of Protease-activated Receptors in the Vascular System

Altered Vascular Injury Responses in Mice Deficient in Protease-Activated Receptor-1

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