IMMEDIATE POSTNATAL RAT-HEART DEVELOPMENT MODIFIED BY ABDOMINAL AORTIC BANDING - ANALYSIS OF GENE-EXPRESSION

Proliferative growth of the ventricular myocyte (cardiomyocyte) is pri marily limited to embryonic, fetal and very early neonatal periods of heart development. In contrast, cardiomyocyte maturation, as evidenced by cellular hypertrophy, is a long-term process that can occupy the b ulk of the life-span of the mature organism. As the newborn myocyte un dergoes a 'transition' from proliferative to hypertrophic growth, vent ricular remodeling of the non-myocyte compartment is characterized by increased extracellular matrix (ECM) formation and coronary capillary angiogenesis. A role for ventricular-derived growth factors (GFs) in t hese inter-related processes are examined in an animal model of altere d heart development produced by neonatal aortic banding. The suprarena l abdominal aorta of five day old rat pups were banded (B), sham opera ted (S), or untreated (C) and ventricular tissue (left ventricular fre e wall and septum) obtained at 7-, 14-, and 21-days post-intervention. Using Northern blot RNA hybridizations, expression of growth factors (GFs) and/or GF-receptors (GFR's) temporally associated with heart dev elopment were evaluated. Transcript levels for TGF-beta(1) IGF-II, and their associated cell surface receptors were increased in B animals. Concomitant changes in extracellular matrix (ECM) genes (as evaluated by Collagens Type I, III, and IV) were also increased in B animals. In addition, transcript levels for the vascular morphogenesis and remode ling-related protein SPARC (Secreted Protein, Acidic and Rich in Cyste ine) was also elevated in the B animals. In several instances, S anima ls demonstrated changes in steady state transcript levels for genes wh ich may influence myocyte maturation during the postnatal period. This suggests that normal autocrine/paracrine growth regulatory stimuli an d responses can be modified (by surgical intervention and/or abdominal aortic banding) and these perturbations in gene expression may be rel ated to previously documented changes in myocyte cell number, vascular composition, and ventricular architecture of the banded, neonatal hea rt. Future studies using this model will provide an opportunity to eva luate and possibly identify the stimuli and signal transduction machin ery that regulate the final phases of myocyte proliferation, stimulate capillary formation and ECM deposition, and orchestrate the transitio n to hypertrophic growth during heart development.