Cyclooxygenase-2 in Myocardium Stimulation by Angiotensin-II in Cultured Cardiac Fibroblasts and Role at Acute Myocardial Infarction

Scheuren, Nicole; Jacobs, Martina; Ertl, Georg; Schorb, W

doi:10.1006/jmcc.2001.1484

Cited by 55 publications

(54 citation statements)

References 29 publications

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“…While COX-1 is already present in the healthy coronary vasculature (46,50), COX-2 is mainly induced by shear stress and at sites of inflammation and could therefore become more important after MI. Indeed, studies in humans (50) and rats (43) found an increase in COX-2 in the infarcted myocardium and border zone, and the contribution of prostanoids to regulation of coronary vascular tone in humans increases with the progression of coronary artery disease. Distal to angiographically minimally diseased coronary arteries, inhibition of prostanoid production induces mild vasoconstriction at rest that increases during exercise (8), whereas vasoconstriction is most pronounced in patients with coronary artery disease at rest (18,22,39) and during exercise (18,39).…”

Section: Integrated Endothelial Control Of Coronary Resistance Vesselmentioning

confidence: 99%

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

Beer

Taverne

Kuster

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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de Beer VJ, Taverne YJ, Kuster DW, Najafi A, Duncker DJ, Merkus D. Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction. Am J Physiol Heart Circ Physiol 301: H1080 -H1089, 2011. First published June 17, 2011 doi:10.1152/ajpheart.01307.2010 is associated with endothelial dysfunction resulting in an imbalance in endothelium-derived vasodilators and vasoconstrictors. We have previously shown that despite increased endothelin (ET) plasma levels, the coronary vasoconstrictor effect of endogenous ET is abolished after MI. In normal swine, nitric oxide (NO) and prostanoids modulate the vasoconstrictor effect of ET. In light of the interaction among NO, prostanoids, and ET combined with endothelial dysfunction present after MI, we investigated this interaction in control of coronary vasomotor tone in the remote noninfarcted myocardium after MI. Studies were performed in chronically instrumented swine (18 normal swine; 13 swine with MI) at rest and during treadmill exercise. Furthermore, endothelial nitric oxide synthase (eNOS) and cyclooxygenase protein levels were measured in the anterior (noninfarcted) wall of six normal and six swine with MI. eNOS inhibition with N -nitro-L-arginine (L-NNA) and cyclooxygenase inhibition with indomethacin each resulted in coronary vasoconstriction at rest and during exercise, as evidenced by a decrease in coronary venous oxygen levels. The effect of L-NNA was slightly decreased in swine with MI, although eNOS expression was not altered. Conversely, in accordance with the unaltered expression of cyclooxygenase-1 after MI, the effect of indomethacin was similar in normal and MI swine. L-NNA enhanced the vasodilator effect of the ETA/B receptor blocker tezosentan but exclusively during exercise in both normal and MI swine. Interestingly, this effect of L-NNA was blunted in MI compared with normal swine. In contrast, whereas indomethacin increased the vasodilator effect of tezosentan only during exercise in normal swine, indomethacin unmasked a coronary vasodilator effect of tezosentan in MI swine both at rest and during exercise. In conclusion, the present study shows that endothelial control of the coronary vasculature is altered in post-MI remodeled myocardium. Thus the overall vasodilator influences of NO as well as its inhibition of the vasoconstrictor influence of ET on the coronary resistance vessels were reduced after MI. In contrast, while the overall prostanoid vasodilator influence was maintained, its inhibition of ET vasoconstrictor influences was enhanced in post-MI remote myocardium. endothelin; nitric oxide; prostacyclin CONGESTIVE HEART FAILURE IS the only major cardiovascular disorder of which the incidence has increased over the past decade, which is principally due to a reduction in mortality associated with acute myocardial infarction (MI). Consequently, MI has become an increasingly important risk factor for the development of congestive heart failure (5). The loss of viable myocardial tissue and the consequent left ve...

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Section: Integrated Endothelial Control Of Coronary Resistance Vesselmentioning

confidence: 99%

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

Beer

Taverne

Kuster

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…In a study in rats, it was shown that treatment with a COX-2 inhibitor during MI reduced fibroblast proliferation, macrophage infiltration, and inflammation in the heart. 32 Thus we hypothesize that the reduction in hypertrophy and fibrosis may not have a beneficial effect if the overall level of inflammation in the heart is not appropriately regulated. This is an area for future studies.…”

Section: Qian Et Al Ep 4 Effects On Cardiac Remodelingmentioning

confidence: 99%

Reduced Cardiac Remodeling and Function in Cardiac-Specific EP ₄ Receptor Knockout Mice With Myocardial Infarction

et al. 2008

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Abstract-We have shown previously that cyclooxygenase-2 inhibition reduces cardiac hypertrophy and fibrosis postmyocardial infarction (MI) in a mouse model and that prostaglandin E 2 stimulates cardiomyocyte hypertrophy in vitro through its EP 4 receptor. Because the role of cardiac myocyte EP 4 in cardiac function and hypertrophy in vivo is unknown, we generated mice lacking EP 4 only in cardiomyocytes (CM-EP 4 knockout [KO]). Twelve-to 14-week-old mice were evaluated using echocardiography and histology. There were no differences in ejection fraction, myocyte cross-sectional area, and interstitial collagen fraction between KO mice and littermate controls. To test the hypothesis that EP 4 is involved in cardiac remodeling after MI, we induced MI by ligating the left anterior descending coronary artery. Two weeks later, the mice were subjected to echocardiography, and hearts were removed for histology and Western blot. There was no difference in infarct size between KO mice and controls; however, KO mice showed less myocyte cross-sectional area and interstitial collagen fraction than controls. Also, CM-EP4 KO mice had reduced ejection fraction. Because the transcription factor Stat-3 is involved in hypertrophy and protection from ischemic injury, we tested whether it was activated in control and KO mouse hearts after MI. Western blot indicated that Stat-3 was activated in control hearts after MI but not in KO hearts. Thus, CM-EP4 deletion decreased hypertrophy, fibrosis, and activation of Stat-3. However, cardiac function was unexpectedly worsened in these mice. We conclude that cardiac myocyte EP 4 plays a role in hypertrophy via activation of Stat-3, a process that seems to be cardioprotective.

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“…Selective COX-2 inhibition has also been suggested to improve cardiac function when given after the period of acute infarction in some experimental rodent models. 21 When rofecoxib was given before and during the period of acute infarction in one such model, 22 a reduction in macrophage infiltration and fibroblast proliferation was observed without significant effect on infarct size. COX-2 expression in isolated cardiac fibroblasts was dependent on angiotensin II and P38 mitogen-activated protein kinase.…”

Section: Can Selective Cox-2 Inhibition Reduce Cardiovascular Events?mentioning

confidence: 99%

“…COX-2 expression in isolated cardiac fibroblasts was dependent on angiotensin II and P38 mitogen-activated protein kinase. 22 Further support for a possible beneficial role of selective COX-2 inhibition on cardiovascular events comes from the Nonsteroidal Anti-Inflammatory Drugs in Unstable Angina Treatment-2 (NUT-2) pilot study by Altman et al 23 in this issue of Circulation. In this study, the COX-2 inhibitor meloxicam was administered intravenously and continued orally for 30 days.…”

Section: Can Selective Cox-2 Inhibition Reduce Cardiovascular Events?mentioning

confidence: 99%

Cyclooxygenase-2 Inhibition and Cardiovascular Events

2002

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Cyclooxygenase-2 in Myocardium Stimulation by Angiotensin-II in Cultured Cardiac Fibroblasts and Role at Acute Myocardial Infarction

Cited by 55 publications

References 29 publications

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

Reduced Cardiac Remodeling and Function in Cardiac-Specific EP ₄ Receptor Knockout Mice With Myocardial Infarction

Cyclooxygenase-2 Inhibition and Cardiovascular Events

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Cyclooxygenase-2 in Myocardium Stimulation by Angiotensin-II in Cultured Cardiac Fibroblasts and Role at Acute Myocardial Infarction

Cited by 55 publications

References 29 publications

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

Reduced Cardiac Remodeling and Function in Cardiac-Specific EP 4 Receptor Knockout Mice With Myocardial Infarction

Cyclooxygenase-2 Inhibition and Cardiovascular Events

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Product

Resources

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Reduced Cardiac Remodeling and Function in Cardiac-Specific EP ₄ Receptor Knockout Mice With Myocardial Infarction