Titin isoform expression in normal and hypertensive myocardium.
OBJECTIVE
Titin isoform expression patterns were examined to explain previously observed genetic differences in rat cardiac passive tension.


METHODS
Rat ventricles from male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats (normotensive) were used to analyze the titin isoform patterns. The hypertensive status was verified by blood pressure measurements and heart weight to body weight ratios. Gel electrophoresis and scanning densitometry were performed to determine ratios of myosin heavy chain and titin isoforms expressed. In situ hybridization using a cRNA probe specific for N2BA titin and a positive control in the N2B unique region was used to demonstrate tissue location of the titin message.


RESULTS
Regression analysis of titin isoform ratios, myosin heavy chain isoform ratios, and heart weight to body weight ratios all suggest a smaller proportion of N2BA titin (longer isoform) was expressed in rat left ventricles with increased hypertrophy. In situ hybridization showed that the N2BA and N2B isoforms were co-expressed within most of the cardiomyocytes. Agarose gel electrophoresis demonstrated two different N2BA titin isoforms in all rat ventricles.


CONCLUSIONS
Expression of less N2BA and more N2B titin in response to pressure overload will result in higher passive tension upon stretch at a given sarcomere length and thus affect cardiac performance.
Warren
Chad M
CM
Muscle Biology Laboratory, University of Wisconsin-Madison, 1805 Linden Dr. West, Madison, WI 53706, USA.
Jordan
Maria C
MC
Roos
Kenneth P
KP
Krzesinski
Paul R
PR
Greaser
Marion L
ML
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001835:Body Weight; D064211:Connectin; D003720:Densitometry; D004587:Electrophoresis, Agar Gel / Q000379:methods; D006973:Hypertension / Q000378:metabolism*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009124:Muscle Proteins / Q000032:analysis*; D009206:Myocardium / Q000737:chemistry*; D018995:Myosin Heavy Chains / Q000032:analysis; D009929:Organ Size; D020033:Protein Isoforms / Q000032:analysis*; D011494:Protein Kinases / Q000032:analysis*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020257:Ventricular Remodeling
D064211:Connectin; D009124:Muscle Proteins; D020033:Protein Isoforms; D011494:Protein Kinases; D018995:Myosin Heavy Chains