Rosenkranz-Weiss P, Tomek R J, Mathew J, Eghbali M
Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06510.
J Mol Cell Cardiol. 1994 Feb;26(2):261-70. doi: 10.1006/jmcc.1994.1029.
Sex-related differences in predisposition to heart diseases have long been recognized. The molecular and cellular bases for this difference are unknown. In this study we have compared expression of genes for various structural and functional proteins of muscle and interstitial compartments of the myocardium in the adult and neonatal, male and female rat heart. We have also compared cultured cardiac fibroblasts from male and female hearts with regards to gene expression and proliferative capacity. We showed that in the adult rats, the abundance of mRNAs for contractile proteins alpha- and beta-myosin heavy chain (MHC) is higher in the heart of female rats than in that of age-matched male rats. However, the difference in mRNA level for alpha-MHC was more drastic (736%, P < 0.001) than that for beta-MHC (469%, P < 0.001). mRNA levels for sarcomeric actin in the female heart were greater by 79% (P < 0.001). Collagen type I had a significantly higher (303%, P < 0.01) mRNA level in the female heart compared with the male heart. mRNAs for TGF-beta 1, cytoskeletal actin and connexin 43 were also higher (150%, P < 0.01; 130%, P < 0.01, and 150%, P < 0.01, respectively) in the female heart compared with age-matched male heart. There were no significant sex-related differences at the mRNA levels for the above proteins in ventricular tissue from neonatal male and female littermates. At the cellular level, cardiac fibroblasts obtained from adult and neonatal hearts of both sexes were comparable with respect to the abundance of mRNAs for collagen type I, TGF-beta 1 or cytoskeletal actin. However, DNA synthesis, as measured by [3H]thymidine incorporation, was higher (328%, P < 0.01) in cells from adult female heart compared with that in cells from adult male rat heart. This difference was even more pronounced in cardiac fibroblasts obtained from newborn female rats (933%, P < 0.001) compared with that in cells obtained from newborn male rat hearts. Together, these findings show that there are sex-related differences in gene expression for most major proteins in heart tissue and that this phenomenon is associated with the post-pubertal period. These findings further suggest that sex-related differential gene expression and DNA synthesis in cardiac cells are due to the regulatory effects of male- and female-specific hormones.
长期以来，人们已经认识到心脏病易感性存在性别差异。但这种差异的分子和细胞基础尚不清楚。在本研究中，我们比较了成年和新生雄性及雌性大鼠心脏中心肌的肌肉和间质成分中各种结构和功能蛋白的基因表达。我们还比较了来自雄性和雌性心脏的培养心脏成纤维细胞的基因表达和增殖能力。我们发现，在成年大鼠中，雌性大鼠心脏中收缩蛋白α-和β-肌球蛋白重链（MHC）的mRNA丰度高于年龄匹配的雄性大鼠。然而，α-MHC的mRNA水平差异（736%，P<0.001）比β-MHC（469%，P<0.001）更为显著。雌性心脏中肌节肌动蛋白的mRNA水平高79%（P<0.001）。与雄性心脏相比，雌性心脏中I型胶原蛋白的mRNA水平显著更高（303%，P<0.01）。与年龄匹配的雄性心脏相比，雌性心脏中TGF-β1、细胞骨架肌动蛋白和连接蛋白43的mRNA水平也更高（分别为150%，P<0.01；130%，P<0.01和150%，P<0.01）。新生雄性和雌性同窝仔鼠心室组织中上述蛋白质的mRNA水平没有显著的性别差异。在细胞水平上，从成年和新生两性心脏获得的心脏成纤维细胞在I型胶原蛋白、TGF-β1或细胞骨架肌动蛋白的mRNA丰度方面相当。然而，通过[3H]胸苷掺入法测定的DNA合成，成年雌性心脏来源的细胞比成年雄性大鼠心脏来源的细胞更高（328%，P<0.01）。与新生雄性大鼠心脏来源的细胞相比，新生雌性大鼠心脏来源的心脏成纤维细胞中的这种差异更为明显（933%，P<0.001）。总之，这些发现表明心脏组织中大多数主要蛋白质的基因表达存在性别差异，并且这种现象与青春期后时期有关。这些发现进一步表明，心脏细胞中性别相关的差异基因表达和DNA合成是由于雄性和雌性特异性激素的调节作用。
