Molecular Signaling in Myocardial Hypertrophy and Heart Failure

Abstract

In hoth humans and animal models. chronic pressure overload is associah.•d with functional decompensation or the heart and poor clinical ( lltcomc accompanied with subtle alterations in energetic and contractile functions. The complications resulting from hypertension include the onset of left ventricular hypertrophy (LVII). cardiac failure and ischnemic heart disease. The apparent biological response at the gene level is revision to a fetal program of cardiac gene expression which eventually leads to progressive contractile dysfunction followed by transition to heart failure. Many growth factors evoke the expression of proto-oncogenes and immediate early genes, which are also rapidly,O and transiently activated in response to hypertrophy associated signals in cardiac cells. Emerging among the multitude of such factors. angiotensin II (Angll), well characterized octapeptide driven from the prohormone angiotensinogen (ANG)).

Recent data suppOrt the notion that the expression of specific transcription factors is modulated in response to hypertrophy related signals which execute changes at the gene level affecting the enrichment of certain proteins. Signal transduction pathways that are ac.tiva:ed in cardiac hypertrophy induced in vivo by pressure overload are also linked to uprcgulation of the autocrinc 1\ngii loop. Dramatic increase in sign;,li tr;,msduction ami activ;,1tor of transcription (STi\TJ proteins in spontaneously hypertensive rat (SIIR) heart uncover a novel mechanism by which the activation of selective sets of STATs underlies the mobilization of the gene activating program intrinsic- to cardiac hypertrophy.