Document Detail


KS370G, a synthetic caffeamide derivative, improves left ventricular hypertrophy and function in pressure-overload mice heart.
MedLine Citation:
PMID:  22484506     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cardiac hypertrophy is an important compensatory mechanism in response to a pressure overload, but a sustained excessive cardiac workload may deteriorate to maladaptive hypertrophy and to increased risk of heart failure. In this study, we evaluated the effects of KS370G on left ventricular hypertrophy and function. Abdominal aortic banding was performed by constricting the abdominal aorta. Hypertrophied heart was studied at 8weeks after the operation. After the operation, KS370G 1mg/kg (K1 group) was administered by oral gavage once a day. Left ventricular function was measured by a 1.2F pressure-volume catheter (Scisense, Canada). The levels of protein for α-SMA (smooth muscle actin), p-AKT (protein kinase B), p-GSK3β (glycogen synthase kinase 3β) and p-ERKs (extracellular signal-regulated kinases) in myocardium were analyzed by Western blot. Plasma levels of angiotensin II, atrial natriuretic peptide and lactate dehydrogenase were analyzed by commercial kits. H.E. staining and M.T. staining methods were also used to observe diameter of cardiomyocytes and collagen accumulation. Chronic oral treatment with 1mg/kg KS370G inhibited cardiac hypertrophy and improved cardiac function induced by pressure overload. KS370G also decreased the plasma levels of atrial natriuretic peptide and lactate dehydrogenase. Besides, pressure overload-induced increase of α-SMA and phosphorylation of ERK, AKT and GSK3β were significantly reduced by chronic oral treatment with KS370G. We also found that chronic oral treatment with KS370G reduced cardiac collagen accumulation. KS370G improved left ventricular function and inhibited cardiac hypertrophy through the decrease of the phosphorylation of ERK, AKT and GSK3β in pressure-overload mice heart.
Authors:
Yi-Chun Weng; Cheng-Fung Chuang; Sung-Ting Chuang; Hsi-Lin Chiu; Yueh-Hsiung Kuo; Ming-Jai Su
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-29
Journal Detail:
Title:  European journal of pharmacology     Volume:  -     ISSN:  1879-0712     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-4-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Institute of Pharmacology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Rd., Taipei, Taiwan.
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