Gender differences in molecular remodeling in pressure overload hypertrophy

OBJECTIVES The objective of this study was to examine gender differences in left ventricular (LV) function and expression of cardiac genes in response to LV pressure overload due to ascending aortic stenosis in rats. BACKGROUND Clinical studies have documented gender differences in the patte rn of adaptive LV hypertrophy. Whether these differences result from intrin sic differences in molecular adaptation to pressure overload between men an d women, or are related to other factors is not known. METHODS Male (n = 8) and female (n = 8) Wistar rats underwent ascending aor tic stenosis and were studied 6 weeks after banding with gender-matched con trol rats (male n = 7; female n = 7). The LV contractile reserve was examin ed in isolated hearts from each group. We compared LV messenger ribonucleic acid (mRNA) levels of atrial natriuretic factor (ANF), beta-myosin heavy c hain, sarcoplasmic reticulum Ca2+-adenosine triphosphatase (ATPase) and Na-Ca2+ exchanger. Reverse transcriptase polymerase chain reaction was used t o identify estrogen receptor transcript in cardiac myocytes and LV tissue. RESULTS The magnitude of LV hypertrophy (LVH) and systolic wall stress were similar in male and female animals with LVH. Male LVH hearts demonstrated a depressed contractile reserve; in contrast, contractile reserve was prese rved in female LVH hearts. The expression of beta-myosin heavy chain and AN F mRNA was greater in male versus female LVH hearts. Sarcoplasmic reticulum Ca2+ -ATPase mRNA levels were depressed in male LVH but not in female LVH compared with control rats, and Na+-Ca2+ exchanger mRNA levels were increas ed similarly in both male and female LVI-I hearts. Estrogen receptor transc ript was detected in both adult male and female cardiac myocytes and LV tis sue. CONCLUSIONS There are significant gender differences in the LV adaptation t o pressure overload despite a similar degree of LVH and systolic wall stres s in male and female rats. There is the potential for estrogen signaling th rough the adult myocyte estrogen receptor in both male and female rats to c ontribute to gender differences in gene expression in pathologic hypertroph y. (C) 1999 by the American College of Cardiology.