Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
J Cell Biochem. 2012 Oct;113(10):3276-87. doi: 10.1002/jcb.24206.
Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS), an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte-derived secretory factor, are associated with cardiac remodeling. Deficiency of eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso-protective, anti-inflammatory, and anti-atherogenic properties. We hypothesized that increased levels of adiponectin would alleviate cardiac pathology resulting from eNOS deficiency, while decreased levels of adiponectin would exacerbate the pathology. Male and female mice, deficient in eNOS, and either lacking or over-expressing adiponectin, were fed high fat diet (HFD) or normal chow. Cardiac magnetic resonance imaging was performed to serially assess heart morphology and function up to 40 weeks of age. Thirty-two weeks of HFD feeding led to significantly greater LV mass in male mice deficient in eNOS and either lacking or over-expressing adiponectin. Heart function was significantly reduced when the mice were deficient in either eNOS, adiponectin or both eNOS and adiponectin; for female mice, heart function was only reduced when both eNOS and adiponectin were lacking. Thus, while over-expression of adiponectin in the eNOS deficient HFD fed male mice preserved function at the expense of significantly increased LV mass, female mice were protected from decreased function and increased LVH by over-expression of adiponectin. Our results demonstrate a sexual dimorphism in response of the heart to alterations in eNOS and adiponectin during high fat feeding and suggest that adiponectin might require eNOS for some of its metabolic effects.
左心室肥厚（LVH）是心血管疾病的一个危险因素，也是主要的死亡原因。参与调节血管张力的内皮型一氧化氮合酶（eNOS）和脂肪细胞衍生的分泌因子脂联素的改变与心脏重构有关。eNOS 的缺乏与高血压和 LVH 有关。脂联素具有血管保护、抗炎和抗动脉粥样硬化作用。我们假设脂联素水平的升高将减轻 eNOS 缺乏引起的心脏病理学，而脂联素水平的降低将加剧病理学。缺乏 eNOS 的雄性和雌性小鼠，缺乏或过表达脂联素，分别给予高脂肪饮食（HFD）或正常饮食。心脏磁共振成像（CMR）用于连续评估心脏形态和功能，直至 40 周龄。32 周的 HFD 喂养导致缺乏 eNOS 且缺乏或过表达脂联素的雄性小鼠的左心室质量显著增加。当小鼠缺乏 eNOS、脂联素或两者时，心脏功能显著降低；对于雌性小鼠，只有当 eNOS 和脂联素都缺乏时，心脏功能才会降低。因此，虽然在缺乏 eNOS 的 HFD 喂养雄性小鼠中过表达脂联素以牺牲显著增加的 LV 质量为代价保存了功能，但雌性小鼠通过过表达脂联素免受功能下降和 LVH 增加的影响。我们的结果表明，在高脂肪喂养期间，eNOS 和脂联素的改变对心脏的反应存在性别二态性，并表明脂联素可能需要 eNOS 来发挥其部分代谢作用。
