Expression of Endothelin-1 and Endothelin-Converting Enzyme-1 mRNAs and Proteins in Failing Human Hearts

Fukuchi, Mitsumasa; Giaid, Adel

doi:10.1097/00005344-199800001-00120

Cited by 44 publications

(25 citation statements)

References 13 publications

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“…20 Importantly, the potentiation of exogenous and endogenous ET-1 effects seen in endotoxemia appeared to be unrelated to alteration in ET A receptor density or sensitivity. Our study also confirmed sepsis-induced increases in plasma ET-1 concentration as previously described 21,22 and showed that septic heart was unlikely to be the source of increased ET-1 production, because a similar pattern of ET-1 staining was found in control and septic hearts.…”

Section: Discussionsupporting

confidence: 91%

Activation of Cardiac Endothelium as a Compensatory Component in Endotoxin-Induced Cardiomyopathy

et al. 2001

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Background-In view of growing evidence of an important endothelial paracrine regulation of cardiac function, the present study investigated the role of cardiac endothelium-derived endothelin-1 (ET-1), prostaglandins, and nitric oxide (NO) during endotoxin-induced cardiomyopathy in rabbits. Methods and Results-Immunohistochemical studies showed a marked transient coinduction of the inducible isoforms of NO synthase (NOS-2) and cyclooxygenase (COX-2) in endocardial endothelium and coronary arteriolar endothelium of hearts 12 hours after intravenous administration of lipopolysaccharide (LPSϩ12h); staining for both isoforms was much weaker 24 hours later (LPSϩ36h). Nitrotyrosine localization was similar to that of NOS-2, suggesting a NOS-2-related endothelial formation of peroxynitrite in septic hearts. Contractile performance of papillary muscles was depressed in both LPS-treated groups. In the LPSϩ12h group, however, isometric twitches were significantly prolonged (482Ϯ14 versus 420Ϯ14 ms in the saline-treated group, PϽ0.005). This twitch prolongation was completely reversed by simultaneous administration of BQ-123 and indomethacin to block endogenous ET-1 and prostaglandins, respectively. In addition, in the LPSϩ12h group, myocardial inotropic responsiveness to exogenous ET-1 was enhanced (PϽ0.01). Conclusions-Cardiac

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Section: Discussionsupporting

confidence: 91%

Activation of Cardiac Endothelium as a Compensatory Component in Endotoxin-Induced Cardiomyopathy

et al. 2001

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“…Preproendothelin-1 has been more extensively studied and documented in vascular endothelial cells, as well as smooth muscle cells, heart, lung, kidney, brain, and skin (27)(28)(29). Increased endothelin expression has been reported in pulmonary hyper- tension (36), myocardial ischemia (37), and congestive heart failure (38). These are conditions associated with elevated elastase activity where it would be advantageous to assess the possible protective effects of very high levels of elafin expression.…”

Section: Discussionmentioning

confidence: 99%

Targeted overexpression of elafin protects mice against cardiac dysfunction and mortality following viral myocarditis

Zaidi¹,

Hui²,

Cheah³

et al. 1999

J. Clin. Invest.

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Serine elastases degrade elastin, stimulate vascular smooth muscle cell migration and proliferation, and are associated with myocardial damage. To evaluate the impact of elastase inhibition on cardiovascular development and disease, transgenic mice were created in which the mouse preproendothelin-1 promoter was used to target elafin overexpression to the cardiovascular system. To distinguish the transgene from endogenous elafin, constructs were made incorporating a FLAG sequence; the COOH-terminus FLAG-tagged elafin construct produced a stable, functionally active gene product and was used to create transgenic mice. Consistent with endothelin expression, abundant elafin mRNA was observed in transgenic F1 embryos (embryonic day 13.5) and in adult transgenic mice heart, trachea, aorta, kidney, lung, and skin, but not in liver, spleen, and intestine. Functional activity of the transgene was confirmed by heightened myocardial elastase inhibitory activity. No tissue abnormalities were detected by light microscopy or elastin content. However, injection of 10 plaque-forming units (PFU) of encephalomyocarditis virus resulted in death within 11 days in 10 out of 12 nontransgenic mice compared with one out of nine transgenic littermates. This reduced mortality was associated with better cardiac function and less myocardial inflammatory damage. Thus, elafin expression may confer a protective advantage in myocarditis and other inflammatory diseases.

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“…and endothelial cells, and cardiomyocytes express high affinity ET-1 binding sites [4,5,6]. ET-1 induces contraction and increases inotropy of cardiomyocytes.…”

Section: Immunohistologymentioning

confidence: 99%

ACE-inhibition is superior to endothelin A receptor blockade in preventing abnormal capillary supply and fibrosis of the heart in experimental diabetes

et al. 2004

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Aims/hypothesis. There is little information whether cardiac capillary supply is deranged in diabetes. Hyperglycaemia is a potent stimulus for endothelin-1 (ET-1) production. We therefore hypothesised that increased ET-1 production in Streptozotocin-induced Type 1 diabetes causes abnormalities of cardiac capillaries and the aorta. To this end we compared the effects of an ET receptor A blocker (ET A -RB) with that of an ACE-inhibitor (ACE-i) or their combination in rats with Streptozotocin (STZ) diabetes. Methods. Sprague Dawley rats were injected with 65 mg STZ i.v. and subsequently developed diabetes. Rats were left untreated or received daily either the ACE-i Trandolapril, the ET A -RB Darusentan or a combination of both. After 6 months the experiment was terminated and the heart and the aorta were investigated using quantitative morphological techniques. Results. ACE-i but not ET A -RB lowered blood pressure in STZ Type 1 diabetic rats. Capillary length density was lower in untreated STZ diabetic rats (2932±128 mm/mm 3 ) compared to non-diabetic control rats (3410±252 mm/mm 3 ). Treatment with ACE-i (3568±431 mm/mm 3 ), but not with ET A -RB (2893±192 mm/mm 3 ), prevented the decrease in capillary supply. Volume density of the myocardial interstitium was higher in untreated STZ diabetic rats (0.86±0.04%) compared to non-diabetic control rats (0.36±0.06%). In all three intervention groups the values were lower (ACE-i: 0.53±0.05%, ET A -RB: 0.7±0.08% and combination: 0.69±0.1). Conclusion/interpretation. Our study identifies a capillary defect of the heart in STZ diabetes, i.e. decreased capillary supply. This abnormality was reversed by ACE-i, but not by ET A -R blockade. A similar trend, although not complete normalisation, was seen in cardiac fibrosis. [Diabetologia (2004) 47:316-324]

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Expression of Endothelin-1 and Endothelin-Converting Enzyme-1 mRNAs and Proteins in Failing Human Hearts

Cited by 44 publications

References 13 publications

Activation of Cardiac Endothelium as a Compensatory Component in Endotoxin-Induced Cardiomyopathy

Activation of Cardiac Endothelium as a Compensatory Component in Endotoxin-Induced Cardiomyopathy

Targeted overexpression of elafin protects mice against cardiac dysfunction and mortality following viral myocarditis

ACE-inhibition is superior to endothelin A receptor blockade in preventing abnormal capillary supply and fibrosis of the heart in experimental diabetes

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