title: Titin isoform expression in aortic stenosis.
abstract: Titin is a giant sarcomeric protein that plays a major role in determining passive myocardial stiffness. The shorter N2B isoform results in a higher passive myocardial stiffness than the longer N2BA isoform. We hypothesised that the expression of the short N2B isoform would be increased in patients with aortic stenosis compared with healthy controls in response to pressure overload, in order to act as a modulator for the increased demand placed on the left ventricle during the early stages of the hypertrophic response. Myocardial biopsies were obtained from the left ventricle of 19 patients undergoing aortic valve replacement for aortic stenosis who had no significant co-existing coronary artery disease. Left ventricular biopsies were also obtained from 13 donor hearts for comparison. SDS-agarose gels revealed small N2B and large N2BA cardiac titin isoforms, with a mean N2BA/N2B ratio that was significantly decreased in the 19 aortic stenotic patients compared with the 13 controls (0.66+/-0.04 in the normal donor hearts compared with 0.48+/-0.03 in patients with aortic stenosis; P=0.02). However, total titin remained unchanged (0.28+/-0.02 compared with 0.24+/-0.02 respectively; P=0.29). In conclusion, the expression of less N2BA and more N2B titin in response to pressure overload may result in the generation of higher passive tension upon stretch to a given sarcomere length and this might affect cardiac performance.
authors.affiliation: Department of Cardiovascular Medicine, University of Birmingham, Birmingham, U.K. L.K.Williams@bham.ac.uk
authors.forename: Lynne
authors.initials: L
authors.lastname: Williams
authors.forename: Neil
authors.initials: N
authors.lastname: Howell
authors.forename: Domenico
authors.initials: D
authors.lastname: Pagano
authors.forename: Peter
authors.initials: P
authors.lastname: Andreka
authors.forename: Marton
authors.initials: M
authors.lastname: Vertesaljai
authors.forename: Tiffany
authors.initials: T
authors.lastname: Pecor
authors.forename: Michael
authors.initials: M
authors.lastname: Frenneaux
authors.forename: Henk
authors.initials: H
authors.lastname: Granzier
mesh_terms: D000368:Aged; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D064211:Connectin; D005260:Female; D019918:Heart Valve Prosthesis Implantation; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D012518:Sarcomeres / Q000378:metabolism; D012737:Sex Factors; D013314:Stress, Mechanical; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D064211:Connectin; D009124:Muscle Proteins; D020033:Protein Isoforms; C577285:TTN protein, human; D011494:Protein Kinases