Aortic perfusion pressure as early determinant of beta-isomyosin expression in perfused hearts.
Pressure overload in vivo induces an increase in cardiac protooncogene and stress protein expression that may initiate the long-term genetic changes observed in hypertrophy. To known whether mechanical stimulus is linked to specific gene transcription, expression of immediate early genes and synthesis of total proteins and myosin heavy chains (MHCs) were studied in beating and KCl-arrested isolated rat hearts perfused for 2 h under various coronary pressures. The main result of this study is that in the beating heart an augmentation of aortic pressure from 60 to 120 mmHg results in a pronounced enhancement of the synthesis of MHC (+59%) and of the expression of the beta-MHC isomyosin mRNA (iso-mRNA; +104%). Also, total protein synthesis and the amounts of poly-(A)+, c-fos, c-myc, and heat-shock protein HSP68 mRNAs were increased. To arrest the heart at 60 mmHg has no effect on total protein synthesis and on the amounts of poly(A)+, alpha-MHC and beta-MHC iso-mRNAs, and mRNAs coding for oncoproteins, but the synthesis of MHC decreased by 24%. By contrast with what we have observed in the beating heart, the augmentation of the coronary pressure in the arrested heart stimulates total protein synthesis and increases the amount of poly(A)+, c-fos, c-myc, and HSP68 mRNAs but has no effect on the expression of both MHC iso-mRNAs. In conclusion, the activation of myosin synthesis by high coronary pressure in this model has mainly a pretranslational origin when the heart is beating.(ABSTRACT TRUNCATED AT 250 WORDS)
Delcayre
C
C
Institut National de la Santé et de la Recherche Médicale, Unité 127, Hôpital Lariboisière, Paris, France.
Klug
D
D
Nguyen
V T
VT
Mouas
C
C
Swynghedauw
B
B
D000818:Animals; D001011:Aorta / Q000502:physiology*; D006324:Heart Arrest, Induced; D066298:In Vitro Techniques; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010477:Perfusion; D011061:Poly A / Q000235:genetics; D011312:Pressure; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D009124:Muscle Proteins; D012333:RNA, Messenger; D011061:Poly A; D009218:Myosins