Glycated collagen cross-linking alters cardiac mechanics in volume-overload hypertrophy.
Alteration of hemodynamic loading induces remodeling that includes changes in myocardial properties and extracellular matrix structure. We investigated the hypothesis that cardiac hypertrophy due to volume overload produces changes in myocardial diastolic mechanics and stiffness that are in part due to alterations in advanced glycation end-product (AGE) collagen cross-linking. Rats developed volume overload induced by arteriovenous fistula (AVF). To assess the dependence of AGE cross-linking on mechanics, we prevented AGE formation by administering the drug aminoguanidine (AG) to one group of AVF rats (AG+AVF). Volume overload did not modify collagen concentration. Right ventricular AGE cross-links were modestly elevated in AVF hearts but were significantly reduced by AG. AVF rats exhibited significantly increased septal AGE cross-links that were inhibited in the AG+AVF group. AVF-induced increases in left ventricular longitudinal stiffness and septal circumferential stiffness were prevented in AG+AVF hearts. Volume overload appears to regionally modify AGE collagen cross-linking and stiffness, and AG treatment prevented these increases, demonstrating that AGE cross-linking plays a role in mediating diastolic compliance in volume-overload hypertrophy.
Herrmann
Keith L
KL
Whitaker Institute of Biomedical Engineering, University of California-San Diego, La Jolla, California 92093, USA.
McCulloch
Andrew D
AD
Omens
Jeffrey H
JH
D000818:Animals; D001164:Arteriovenous Fistula; D001696:Biomechanical Phenomena; D001835:Body Weight; D002306:Cardiac Volume; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology*; D003094:Collagen / Q000031:analogs & derivatives* / Q000737:chemistry*; D003187:Compliance; D003432:Cross-Linking Reagents; D003971:Diastole; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000737:chemistry; D006146:Guanidines / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D051381:Rats; D013314:Stress, Mechanical
D003432:Cross-Linking Reagents; D017127:Glycation End Products, Advanced; D006146:Guanidines; C022814:glycosylated collagen; D003094:Collagen; C004479:pimagedine