[Changes in heart genome expression in hypertensive diseases].
Chronic increases in haemodynamic load modify the expression of cardiac genes, leading to cardiac hypertrophy and a new phenotype. As an example, changes in the expression of the genes encoding the main contractile proteins, the isomyosin heavy chains, have been associated with modifications of the physiological properties of cardiac muscle. The cellular and molecular mechanisms which either do or do not initiate and maintain these changes in cardiac genomic expression remain to be elucidated. Using in situ hybridization we show that mRNAs encoding a cellular form of fibronectin (c-FN), a protein of the basal membrane which is not or poorly expressed in adult rat heart, are reexpressed as a result of severe hypertension with a similar time course than the beta-heavy chain of myosin (beta-MHC), also mostly expressed in fetal heart. The accumulation of the c-FN mRNAs was found in the wall of coronary arteries whilst that of the beta-MHC mRNAs occurred in the myocytes at the border zone of these arteries. Thus a high pressure in the arteries could be the trigger inducing the synthesis of factors which could, through a gradient, modulate the phenotype of both the smooth muscle cells of the media and the cardiocytes. Besides, using a model of cultured adult rat cardiocytes, we show that the differential expression of the MHC isoforms is dependent on the beta-adrenergic stimulation but that the regulation depends on the stage of development of the cells and differs for the alpha and beta MHC. These 2 complementary approaches for identifying the molecular mechanisms that control cardiac muscle growth should help for understanding cardiac adaptation triggered by haemodynamic overload, such as arterial hypertension as well as cardiac failure.
Dubus
I
I
Unité INSERM 127, Hôpital Lariboisière, Paris.
Contard
F
F
Marotte
F
F
Samuel
J L
JL
Rappaport
L
L
D000818:Animals; D003285:Contractile Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D005353:Fibronectins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D016678:Genome; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism; D017403:In Situ Hybridization; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D051381:Rats
D003285:Contractile Proteins; D005353:Fibronectins; D007545:Isoproterenol
Changements d'expression du génome cardiaque dans les maladies hypertensives.