Abstract 5941: Gender Differences in Echocardiographic and Gene Expression Patterns of Human Pressure Overload Left Ventricular Hypertrophy
Background. The influence of gender on left ventricular (LV) remodeling under pressure overload associated to aortic valve stenosis (AS) has been long recognized, but the underlying differences in myocardial gene expression patterns have not been explored.
Methods and Results. In 39 patients (21 men, 18 women) operated of AS and 20 surgical controls (9 men, 11 women), we assessed data on echocardiographic LV anatomy and function. Compared to control, AS patients increase absolute and relative wall thicknesses and LV mass index (LVMI), but only men show significant chamber dilation (LVEDDI: Control = 28.6±1.1; AS = 31.8±0.7; p<0.05). Quantitative PCR analysis performed in LV biopsies, revealed significantly increased mRNA expression levels of collagens I and III, fibronectin and TGF-β in AS patients, both women (2.71, 1.84, 1.62 and 1.97 fold, respectively) and men (3.6, 2.34, 2.71 and 1.63 fold, respectively), in comparison with control patients. The myocardial accumulation of fibrous tissue was confirmed in histological sections by Masson trichrome staining. In AS women, collagen I transcriptional upregulation was proportionally higher than other extracellular matrix (ECM) components. MMP-2, TIMP-2 and the MMP-2 to TIMP-2 ratio were not modified. In neither AS gender, myosin heavy chain-β mRNA expression was modified. Both genders increase mRNA levels of myosin light chain-2 (AS men: 1.47 fold; AS women: 1.61 fold), that correlate with the mean aortic transvalvular gradients, but women do so in a significantly greater extent than men for a given gradient value (p<0.05 for slope comparison). LVMI correlated, only in women, with gene expression of sarcomeric proteins. The upregulation of extracellular matrix proteins correlates, only in men, with chamber dilatation and deterioration of LV ejection fraction.
Conclusions. We report qualitative gene expression gender dissimilarities that might be responsible for the LV geometric and functional differences between men and women with AS. These findings further support the need for a gender specific therapeutic approach of pressure overload LVH.