Babiker Fawzi A, Lips Daniel, Meyer Rainer, Delvaux Els, Zandberg Pieter, Janssen Ben, van Eys Guillaume, Grohé Christian, Doevendans Pieter A
Department of Cardiology, Cardiovascular Research Institute Maastricht, University Hospital Maastricht, Netherlands.
Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1524-30. doi: 10.1161/01.ATV.0000223344.11128.23. Epub 2006 Apr 20.
Left ventricular hypertrophy (LVH) displays significant gender-based differences. 17beta-estradiol (E2) plays an important role in this process because it can attenuate pressure overload hypertrophy via 2 distinct estrogen receptors (ERs): ERalpha and ERbeta. However, which ER is critically involved in the modulation of LVH is poorly understood. We therefore used ERalpha-deficient (ERalpha-/-) and ERbeta-deficient (ERbeta-/-) mice to analyze the respective ER-mediated effects.
Respective ER-deficient female mice were ovariectomized and were given E2 or placebo subcutaneously using 60-day release pellets. After 2 weeks, they underwent transverse aortic constriction (TAC) or sham operation. In ERalpha-/- animals, TAC led to a significant increase in ventricular mass compared with sham operation. E2 treatment reduced TAC induced cardiac hypertrophy significantly in wild-type (WT) and ERalpha-/- mice but not in ERbeta-/- mice. Biochemical analysis showed that E2 blocked the increased phosphorylation of p38-mitogen-activated protein kinase observed in TAC-treated ERalpha-/- mice. Moreover, E2 led to an increase of ventricular atrial natriuretic factor expression in WT and ERalpha-/- mice.
These findings demonstrate that E2, through ERbeta-mediated mechanisms, protects the murine heart against LVH.
左心室肥厚（LVH）存在显著的性别差异。17β-雌二醇（E2）在此过程中起重要作用，因为它可通过两种不同的雌激素受体（ERs）：ERα和ERβ减轻压力超负荷引起的肥厚。然而，哪种ER在LVH的调节中起关键作用尚不清楚。因此，我们使用ERα基因敲除（ERα-/-）和ERβ基因敲除（ERβ-/-）小鼠来分析各自ER介导的作用。
分别对ER基因敲除的雌性小鼠进行卵巢切除，并使用60天缓释微丸皮下给予E2或安慰剂。2周后，对它们进行主动脉缩窄（TAC）或假手术。在ERα-/-动物中，与假手术相比，TAC导致心室质量显著增加。E2治疗可显著减轻野生型（WT）和ERα-/-小鼠中TAC诱导的心脏肥厚，但对ERβ-/-小鼠无效。生化分析表明，E2可阻断TAC处理的ERα-/-小鼠中观察到的p38丝裂原活化蛋白激酶磷酸化增加。此外，E2导致WT和ERα-/-小鼠中心房钠尿肽表达增加。
这些发现表明，E2通过ERβ介导的机制保护小鼠心脏免受LVH影响。
