Gender differences in molecular remodeling in pressure overload hypertrophy
EO Weinberg, CD Thienelt, SE Katz, J Bartunek… - Journal of the American …, 1999 - jacc.org
EO Weinberg, CD Thienelt, SE Katz, J Bartunek, M Tajima, S Rohrbach, PS Douglas…
Journal of the American College of Cardiology, 1999•jacc.orgOBJECTIVES 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 pattern of adaptive LV hypertrophy. Whether these
differences result from intrinsic differences in molecular adaptation to pressure overload
between men and women, or are related to other factors is not known. METHODS Male (n …
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 pattern of adaptive LV hypertrophy. Whether these
differences result from intrinsic differences in molecular adaptation to pressure overload
between men and women, or are related to other factors is not known. METHODS Male (n …
Abstract
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 pattern of adaptive LV hypertrophy. Whether these differences result from intrinsic differences in molecular adaptation to pressure overload between men and women, or are related to other factors is not known.
METHODS
Male (n = 8) and female (n = 8) Wistar rats underwent ascending aortic stenosis and were studied 6 weeks after banding with gender-matched control rats (male n = 7; female n = 7). The LV contractile reserve was examined in isolated hearts from each group. We compared LV messenger ribonucleic acid (mRNA) levels of atrial natriuretic factor (ANF), beta-myosin heavy chain, sarcoplasmic reticulum Ca2+–adenosine triphosphatase (ATPase) and Na+–Ca2+exchanger. Reverse transcriptase polymerase chain reaction was used to 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 preserved in female LVH hearts. The expression of beta-myosin heavy chain and ANF 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 increased similarly in both male and female LVH hearts. Estrogen receptor transcript was detected in both adult male and female cardiac myocytes and LV tissue.
CONCLUSIONS
There are significant gender differences in the LV adaptation to pressure overload despite a similar degree of LVH and systolic wall stress in male and female rats. There is the potential for estrogen signaling through the adult myocyte estrogen receptor in both male and female rats to contribute to gender differences in gene expression in pathologic hypertrophy.
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