Estrogen and testosterone have opposing effects on chronic cardiac remodeling and function in mice with myocardial infarction
Estrogen and testosterone have opposing effects on chronic cardiac remodeling and function in mice with myocardial infarction
复制标题
DOI：
10.1152/ajpheart.01087.2002
复制
发表时间：
2003-05-01
影响因子：
4.8
通讯作者：
Yang, XP
中科院分区：
文献类型：
--
作者：
Cavasin, MA;Sankey, SS;Yang, XP
绝经前的女性比同龄男性更不容易患心血管疾病，但绝经后这种优势不再适用。我们以前发现，在心肌梗死（MI）的急性期，雄性小鼠的心脏破裂率明显高于雌性小鼠;然而，性激素对慢性重塑的影响尚不清楚。我们假设雌激素（E）可以保护心肌梗死后心脏免于慢性重塑和功能恶化，而睾酮（T）可能有不良影响。小鼠（4周龄）雌雄各半，分为4组：雌性组：1）假卵巢切除（S-Ovx）+安慰剂（P（S-Ovx + P）、2）S-Ovx + T、3）Ovx + P和4）Ovx + T;雄性组包括1）假阉割（S-Cas）+ P（S-Cas + P）、2）S-Cas +17 β-雌二醇（E）、3）Cas + P和4）Cas + E。6周后诱发心肌梗死。进行超声心动图以评估心脏功能和左心室尺寸（LVD）。在研究结束时测量肌细胞横截面积（MCSA）。在女性中，睾酮和卵巢切除术都降低了射血分数（EF），增加了LVD，当两者结合时，它们进一步加重了心脏功能和重塑。替吉奥显著增加MCSA。在男性中，去势或雌激素增加EF和减少LVD，而去势显着降低MCSA。我们的数据表明，雌激素可预防MI后心脏功能的恶化和重塑，但睾酮可预防心脏功能障碍和重塑，并在雌激素水平降低时具有明显的作用。
Premenopausal women are much less prone to develop cardiovascular disease than men of similar age, but this advantage no longer applies after menopause. We previously found that male mice have a significantly higher rate of cardiac rupture than females during the acute phase of myocardial infarction (MI); however, the effects of sexual hormones on chronic remodeling are unknown. We hypothesized that estrogen (E) may protect the heart from chronic remodeling and deterioration of function post-MI, whereas testosterone (T) may have adverse effects. Mice (4 wk old) of both genders were divided into four groups: female groups consisted of 1) sham ovariectomy (S-Ovx) + placebo (P) (S-Ovx + P), 2) S-Ovx + T, 3) Ovx + P, and 4) Ovx + T; and male groups consisted of 1) sham castration (S-Cas) + P (S-Cas + P), 2) S-Cas + 17beta-estradiol (E), 3) Cas + P, and 4) Cas + E. MI was induced 6 wk later. Echocardiography was performed to assess cardiac function and left ventricular dimensions (LVD). Myocyte cross-sectional area (MCSA) was measured at the end of the study. In females, both testosterone and ovariectomy decreased ejection fraction (EF) and increased LVD, and when combined they aggravated cardiac function and remodeling further. Testosterone significantly increased MCSA. In males, castration or estrogen increased EF and reduced LVD, whereas castration significantly reduced MCSA. Our data suggest that estrogen prevents deterioration of cardiac function and remodeling after MI, but testosterone worsens cardiac dysfunction and remodeling and has a pronounced effect when estrogen levels are reduced.