Increased Immunoreactive Endothelin-1 in Human Transplant Coronary Artery Disease

Ravalli, Stefano; Szabolcs, Matthias; Albala, Arline; Michler, Robert E.; Cannon, Paul J.

doi:10.1161/01.cir.94.9.2096

Cited by 67 publications

(31 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our data corroborate the relationship between heightened perioperative levels of ET-1 and early myocardial dysfunction. In addition, ET-1 has been suggested to play a role in late CAV, and reduced overall survival [25][26][27][28] in clinical cardiac transplantation. ET-1 antagonists improve systolic function in animal models of cardiac transplantation.…”

Section: Discussionmentioning

confidence: 99%

Heart Preservation Using Continuous Ex Vivo Perfusion Improves Viability and Functional Recovery

Ozeki

Kwon

et al. 2007

Circ J

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Heart Preservation Using Continuous Ex Vivo Perfusion Improves Viability and Functional Recovery

Ozeki

Kwon

et al. 2007

Circ J

View full text Add to dashboard Cite

“…3,[7][8][9][10] Endothelial dysfunction is implicated in the development of coronary vasospasm, unstable angina, myocardial infarction, atherosclerosis, and transplant coronary disease. 4,6,8,13,14,19 The normally functioning endothelium maintains ET-1 and NO in balance. Impairment in NO production and/or increased release of ET-1 are key initiators of endothelial dysfunction and injury.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 Elevated ET-1 levels have also been implicated in the development of transplant coronary disease. 4,8,13,14 It is generally accepted that low levels of ET-1 increase NO production; however, recent evidence suggests that elevated levels of ET-1 (as seen after heart failure and ischemia-reperfusion) may impair NO production. 12,15 However, the mechanisms by which elevated levels of ET-1 reduce NO production in endothelial cells have yet to be determined.…”

mentioning

confidence: 99%

Elevated Endothelin-1 Levels Impair Nitric Oxide Homeostasis Through a PKC-Dependent Pathway

et al. 2006

View full text Add to dashboard Cite

Background-Endothelin-1 (ET-1) plays an important role in the maintenance of vascular tone and pathological states such as ischemia/reperfusion (I/R) injury, coronary vasospasm, and cardiac allograft vasculopathy. We assessed the effects of elevated ET-1 levels as seen after I/R to determine if ET-1 modulates nitric oxide (NO) production via the translocation of specific protein kinase C (PKC) isoforms. Methods and Results-Human saphenous vein endothelial cells (HSVECs) (nϭ8) were incubated with ET-1 or phosphate-buffered saline (PBS) for 24 hours. NO production was determined in the supernatant by measuring nitrate/nitrite levels. Protein expression of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), caveolin-1 and PKC were determined. Lastly, PKC translocation and activity were assessed after exposure to the drug of interest. HSVECs exposed to ET-1 displayed decreased NO production. PKC inhibition reduced NO production, whereas PKC activation increased production. NO production was maintained when HSVECs exposed to ET-1 were treated with the PKC agonist, PMA. eNOS protein expression was reduced after ET-1 treatment. PKC inhibition also downregulated eNOS protein expression, whereas PMA upregulated expression. ET-1 exposure led to a significant increase in PKC␦ and PKC translocation compared with control, whereas translocation of PKC was inhibited. ET-1 exposure significantly reduced overall PKC activity compared with control. Conclusions-Our study demonstrates that high levels of ET-1 impair endothelial NO production via an isoform-specific PKC-mediated inhibition of eNOS expression. ET-1 antagonism with bosentan stimulates translocation of PKC and leads to increased PKC activity and NO production. ET-1 antagonism may provide a novel therapeutic strategy to improve vascular homeostasis.

show abstract

“…Because of this disparity in receptor number, the contribution of the ET B receptor to coronary vasoregulation is limited (25). Importantly, ET-1 expression is elevated in atherosclerotic vessels (18,32), and ET-1-mediated vasoconstriction has been implicated in the pathogenesis of atherosclerotic vascular disease, including coronary heart disease (9,20,26,40).…”

mentioning

confidence: 99%

Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults

Stauffer

Westby

Greiner

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Stauffer BL, Westby CM, Greiner JJ, Van Guilder GP, DeSouza CA. Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults. Am J Physiol Regul Integr Comp Physiol 298: R261-R265, 2010. First published November 25, 2009 doi:10.1152/ajpregu.00626.2009.-The prevalence of cardiovascular disease is lower in middle-aged and older women than men. Increased endothelin-1-mediated vasoconstriction has been linked to the etiology of a number of cardiovascular diseases, including atherosclerosis, heart failure, and hypertension. It is unknown whether a sex difference in endothelin-1-mediated vasoconstrictor tone exists in middle-aged and older adults. Therefore, we tested the hypothesis that middle-aged and older men would demonstrate greater ET-1-mediated vasoconstrictor tone than age-matched women. Forearm blood flow in response to intra-arterial infusions of endothelin (ET)-1, BQ-123 (a selective ET A receptor antagonist), and BQ-788 (a selective ETB receptor antagonist) was assessed by venous occlusion plethysmography in 21 women (age: 58 Ϯ 1 yr; body mass index: 26.0 Ϯ 1.0 kg/m 2 ) and 25 men (age: 57 Ϯ 2 yr; body mass index: 26.8 Ϯ 0.7 kg/m 2 ). In response to BQ-123, the increase in forearm blood flow from baseline was significantly higher in the men than the women (24 Ϯ 5% vs. 9 Ϯ 5%; P Ͻ 0.05). In contrast, the increase in forearm blood flow in response to BQ-123 coinfused with BQ-788 was greater in the women than the men, such that the maximum vasodilation to dual endothelin receptor blockade was similar between men and women (ϳ25%). There was no difference in the vasoconstrictor response to ET-1 between the sexes. These results indicate that middle-aged and older men are under greater ET A receptor-mediated vasoconstrictor tone than age-matched women. Since the ET A receptor is the predominant receptor subtype in the coronary vasculature, this sex difference in vasoconstrictor tone may be a mechanism contributing to the sex difference in the prevalence of coronary heart disease in middle-aged and older adults.endothelin-1; endothelin receptor antagonist; endothelium; vascular function; sex differences ENDOTHELIN-1 (ET-1) IS THE most abundant and important vasoconstrictor molecule released from the vasculature. Produced by the endothelium, ET-1 is predominantly released abluminally to activate ET A and ET B receptors located on the vascular smooth muscle causing smooth muscle contraction, cell proliferation, and hypertrophy (35). ET B receptors on the vascular endothelium produce vasodilation via a nitric oxide mechanism and are also a prominent clearance mechanism for circulating ET-1. ET A receptors are the predominant subtype [10 times greater number than ET B (37)] in the arterial system and the coronary arteries, in particular (30, 31, 34). Because of this disparity in receptor number, the contribution of the ET B receptor to coronary vasoregulation is limited (25). Importantly, ET-1 expression is elevated in atherosclerotic vessels (18,32), and ET-1-mediated vasoconstrict...

show abstract

Increased Immunoreactive Endothelin-1 in Human Transplant Coronary Artery Disease

Abstract: Immunoreactivity for ET-1 is significantly increased in TCAD, possibly as a result of stimulatory cytokines and growth factors that are upregulated in the posttransplant state. The results suggest a role for this mitogenic peptide in the pathogenesis of graft arteriosclerosis.

Cited by 67 publications

References 40 publications

Heart Preservation Using Continuous Ex Vivo Perfusion Improves Viability and Functional Recovery

Heart Preservation Using Continuous Ex Vivo Perfusion Improves Viability and Functional Recovery

Elevated Endothelin-1 Levels Impair Nitric Oxide Homeostasis Through a PKC-Dependent Pathway

Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults

Contact Info

Product

Resources

About