Enhancement of Endothelin Converting Enzyme and Endothelin Receptor Subtypes in Human Myocardium with Congestive Heart Failure

2000 ◽  
Vol 6 (S2) ◽  
pp. 608-609
Author(s):  
J. Lin ◽  
C Wei

Endothelin-1 (ET-1) is a potent endothelial cell-drived vasoconstrictive peptide which is increased in congestive heart failure (CHF). ET-1 is converted from its precursor big ET-1 by activation of endothelin converting enzyme (ECE). ET-1 binding to ET-A receptor in vascular smooth muscle cells stimulates vasoconstriction and binding to ET-B receptor in vascular endothelial cells mediates vasodilation. In previous studies, we and others demonstrated that plasma ET-1 was significantly increased in congestive heart failure. However, the presentation and localization of endothelin converting enzyme and endothelin receptors (ET-A and ET-B) in human cardiac tissue with and without heart failure remain unclear. Therefore, the current study was designed to investigate the expression and localization of endothelin receptors and endothelin converting enzyme in human myocardium in the absence or presence of congestive heart failure.Human atrial tissues (n=6) were obtained from normal subjects and end-stage CHF patients during cardiac transplantation. The expression of ECE, ET-A and ET-B were determined by immunohistochemical staining (IHCS).

2000 ◽  
Vol 6 (S2) ◽  
pp. 596-597
Author(s):  
C. Wei ◽  
J. S. McLaughlin

Recent study demonstrated that decrease signal transducer and activator of transcription-3 (STAT3) phosphorylation and increase apoptosis might be a critical point in the transition between compensatory cardiac hypertrophy and heart failure. To date, the protein expression of STAT3 in normal and failing human heart remains unclear. Therefore, the current study was designed to investigate the protein expression of STAT3 in human myocardium with end-stage congestive heart failure (CHF) and compared with that in normal human cardiac tissue.Human cardiac atrial tissue was obtained from normal subjects (n=5) and end-stage CHF patients (n=5) during cardiac transplantation. To detect the DNA fragmentation, in situ terminal deoxymucleotidyl transferase dUTP nick end labeling (TUNEL) was performed. An average of 1000 nuclei was analyzed for TUNEL study. STAT3 protein expression and phosphorylation of STAT3 were determined by immunohistochemical staining (IHCS) with total STAT3 and phospho-specific STAT3 antibodies.


2000 ◽  
Vol 6 (S2) ◽  
pp. 612-613
Author(s):  
S. Ren ◽  
C. Wei

Transforming growth factor-beta (TGF-β) is a growth-regulating peptide that has been shown to enhance collagen production both in vivo and in vitro. The previous studies demonstrated that TGF-β 1 is present in the normal animal myocardium. However, the expression and localization of TGF-β 1 and TGF-P receptor in human myocardium remain unclear. Therefore, the present study was designed to determine the TGF-β 1 and its receptor in human myocardium in normal subjects and in patients with end-stage congestive heart failure (CHF).Human ventricular tissues were obtained from five normal subjects and five patients with end-stage CHF during cardiac transplantation. TGF-β 1 and TGF-beta type I receptor (TGF-βRI) were determined by immunohistochemical staining (IHCS). The results of IHCS was evaluated by staining density scores (0, no staining; 1, minimal staining; 2, mild staining; 3, moderate staining; and 4, strong staining). The positive staining area (+%) in entire section was also determined.


2000 ◽  
Vol 6 (S2) ◽  
pp. 618-619
Author(s):  
P. Y. Lau ◽  
M. G. Cardarelli ◽  
C. Wei

Angiotensin II (AH) is a potent vasoconstrictor and mitogenic factor. AH receptors include type 1 (ATI) and type 2 (AT2) receptors. Recent studies demonstrated that both ATI and AT2 receptors expressed in human myocardium. Circulating and local tissue level of AH was increased in severe congestive heart failure (CHF). However, the expression of ATI and AT2 in cardiac tissue with CHF remains controversial. Therefore, the present study was designed to investigate the protein expression of ATI and AT2 receptors in normal human myocardium and in human cardiac tissue with mild and severe CHF.Human atrial tissues from normal subjects and CHF patients with ischemic cardiomyopathy and dilated cardiomyopathy were obtained from open-heart surgery and cardiac transplantation. ATI and AT2 receptor expression was investigated by immunohistochemical staining (IHCS). The results of IHCS was evaluated by IHCS staining density scores (0, no staining; 1, minimal staining; 2, mild staining; 3, moderate staining; and 4, strong staining).


2003 ◽  
Vol 41 (6) ◽  
pp. 266 ◽  
Author(s):  
Kenneth Dickstein ◽  
Hanka de Voogd ◽  
Milutin Miric ◽  
Roland Willenbrock ◽  
Veselin Mitrovic ◽  
...  

Circulation ◽  
1999 ◽  
Vol 99 (4) ◽  
pp. 570-577 ◽  
Author(s):  
Atsuyuki Wada ◽  
Takayoshi Tsutamoto ◽  
Masato Ohnishi ◽  
Masahide Sawaki ◽  
Daisuke Fukai ◽  
...  

2000 ◽  
Vol 278 (6) ◽  
pp. H2050-H2056 ◽  
Author(s):  
Adviye Ergul ◽  
C. Allyson Walker ◽  
Aron Goldberg ◽  
Simona C. Baicu ◽  
Jennifer W. Hendrick ◽  
...  

Increased plasma levels of endothelin-1 (ET-1) have been identified in congestive heart failure (CHF), but local myocardial interstitial ET-1 levels and the relation to determinants of ET-1 synthesis remain to be defined. Accordingly, myocardial interstitial ET-1 levels and myocyte endothelin-converting enzyme (ECE)-1 activity and expression with the development of CHF were examined. Pigs were instrumented with a microdialysis system to measure myocardial interstitial ET-1 levels with pacing CHF (240 beats/min, 3 wk; n = 9) and in controls ( n = 14). Plasma ET-1 was increased with CHF (15 ± 1 vs. 9 ± 1 fmol/ml, P < 0.05) as was total myocardial ET-1 content (90 ± 15 vs. 35 ± 5 fmol/g, P < 0.05). Paradoxically, myocardial interstitial ET-1 was decreased in CHF (32 ± 4 vs. 21 ± 2 fmol/ml, P < 0.05), which indicated increased ET-1 uptake by the left ventricular (LV) myocardium with CHF. In isolated LV myocyte preparations, ECE-1 activity was increased by twofold with CHF ( P < 0.05). In LV myocytes, both ECE-1a and ECE-1c mRNAs were detected, and ECE-1a expression was upregulated fivefold in CHF myocytes ( P < 0.05). In conclusion, this study demonstrated compartmentalization of ET-1 in the myocardial interstitium and enhanced ET-1 uptake with CHF. Thus a local ET-1 system exists at the level of the myocyte, and determinants of ET-1 biosynthesis are selectively regulated within this myocardial compartment in CHF.


1998 ◽  
Vol 31 ◽  
pp. S31-S34 ◽  
Author(s):  
Zaid Abassi ◽  
Joseph Winaver ◽  
Irith Rubinstein ◽  
Kohei Shimada ◽  
Masaaki Takahashi ◽  
...  

Circulation ◽  
1999 ◽  
Vol 99 (16) ◽  
pp. 2118-2123 ◽  
Author(s):  
Oliver Zolk ◽  
Jessika Quattek ◽  
Gerhard Sitzler ◽  
Thomas Schrader ◽  
Georg Nickenig ◽  
...  

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