GENES MEDIATING CARDIAC REMODELING DURING PREGNANCY AND THE EARLY POST-PARTUM-PERIOD IN MICE
Abstract
The female heart undergoes adaptive remodeling during pregnancy to compensate for the increased hemodynamic load imposed by the developing fetus. However, unlike a similar adaptive process which occurs under pathological conditions (such as hypertension and valvular heart disease) the cardiac changes observed during hypertrophy associated with pregnancy are reversible. The goal of this study is to identify changes in gene expression associated with pregnancy-induced hypertrophy. We tested the hypothesis that pregnancy-induced physiological hypertrophy has a unique genetic signature, likely due to altered hormone levels, which supports and promotes reversible remodeling. Comparing the gene expression profile associated with physiological remodeling with that involved in pathological remodeling of the heart, may lead to new therapeutic approaches for treating pathological heart disease under conditions of increased hemodynamic load. We analyzed two microarray datasets for gene changes during mid and late pregnancy and the early post-partum period and compared them to virgin mice in diestrus. Numerous changes in extracellular matrix genes were identified and the mRNAs for TIMP1-4, MMP3, MMP11, MMP13-MMP16, MMP25, and MMP28 were quantified in left ventricles by real-time PCR confirming some of the microarray changes but not others. Late pregnancy and the early post-partum period exhibited the most gene changes. As changes in TIMP and MMP mRNAs may reflect changes in their protein levels and activity, we predict that MMPs and TIMPs are important players during the peripartum period may determine the extent of matrix remodeling that occurs in the left ventricle during this time.