Document Detail

Alagebrium in combination with exercise ameliorates age-associated ventricular and vascular stiffness.
MedLine Citation:
PMID:  22569357     Owner:  NLM     Status:  MEDLINE    
Advanced glycation end-products (AGEs) initiate cellular inflammation and contribute to cardiovascular disease in the elderly. AGE can be inhibited by Alagebrium (ALT), an AGE cross-link breaker. Moreover, the beneficial effects of exercise on aging are well recognized. Thus, we investigated the effects of ALT and exercise (Ex) on cardiovascular function in a rat aging model. Compared to young (Y) rats, in sedentary old (O) rats, end-systolic elastance (Ees) decreased (0.9±0.2 vs 1.7±0.4mmHg/μL, P<0.05), dP/dt(max) was attenuated (6054±685 vs 9540±939mmHg/s, P<0.05), ventricular compliance (end-diastolic pressure-volume relationship (EDPVR)) was impaired (1.4±0.2 vs 0.5±0.4mmHg/μL, P<0.05) and diastolic relaxation time (tau) was prolonged (21±3 vs 14±2ms, P<0.05). In old rats, combined ALT+Ex (4weeks) increased dP/dt(max) and Ees (8945±665 vs 6054±685mmHg/s, and 1.5±0.2 vs 0.9±0.2 respectively, O with ALT+Ex vs O, P<0.05 for both). Diastolic function (exponential power of EDPVR and tau) was also substantially improved by treatment with Alt+Ex in old rats (0.4±0.1 vs 0.9±0.2 and 16±2 vs 21±3ms, respectively, O with ALT+EX vs O, P<0.05 for both). Pulse wave velocity (PWV) was increased in old rats (7.0±0.7 vs 3.8±0.3ms, O vs Y, P<0.01). Both ALT and Ex alone decreased PWV in old rats but the combination decreased PWV to levels observed in young (4.6±0.5 vs 3.8±0.3ms, O with ALT+Ex vs Y, NS). These results suggest that prevention of the formation of new AGEs (with exercise) and breakdown of already formed AGEs (with ALT) may represent a therapeutic strategy for age-related ventricular and vascular stiffness.
Jochen Steppan; Huang Tran; Alexandre M Benjo; Laxsmi Pellakuru; Viachaslau Barodka; Sungwoo Ryoo; Sineád M Nyhan; Craig Lussman; Gaurav Gupta; Anthony R White; Joao P Daher; Artin A Shoukas; Benjamin D Levine; Dan E Berkowitz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-04-28
Journal Detail:
Title:  Experimental gerontology     Volume:  47     ISSN:  1873-6815     ISO Abbreviation:  Exp. Gerontol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-09-27     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  0047061     Medline TA:  Exp Gerontol     Country:  England    
Other Details:
Languages:  eng     Pagination:  565-72     Citation Subset:  IM    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Department of Anesthesiology & Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
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MeSH Terms
Aging / physiology*
Diastole / physiology
Drug Evaluation, Preclinical / methods
Glycosylation End Products, Advanced / antagonists & inhibitors,  metabolism
Hemodynamics / physiology
Physical Conditioning, Animal / physiology*
Rats, Inbred F344
Systole / physiology
Thiazoles / pharmacology*
Vascular Stiffness / drug effects,  physiology*
Ventricular Function, Left / drug effects,  physiology*
Grant Support
Reg. No./Substance:
0/Glycosylation End Products, Advanced; 0/Thiazoles; DGH49JXB1F/alagebrium

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