Unique cardiovascular Risk Factors in Women Research and Mentoring Progam

描述（由申请人提供）：该项目的目标是指导初级研究人员通过我的研究计划在女性独特的心血管危险因素中进行以患者为导向的研究。指导目标：为了保持我在以病人为导向的研究中的指导计划，继续增加进入这一领域的妇女和少数民族的人数，并允许我的计划在哈佛CTSA内进一步发展。K24将使我能够实现这些目标，让我保持减少临床护理和行政时间，我实现了与原来的K 24奖。研究项目：本申请基于两个转化研究项目：1）确定具有抗盐皮质激素活性的雷公藤红素是否可以改善或预防绝经后妇女雌激素诱导的心血管并发症。对于许多绝经后妇女，血管痉挛症状是生活质量下降的主要原因。雌激素是FDA批准的唯一治疗这些症状的药物。最近的研究表明，雌激素增加心血管疾病（CVD）的风险。因此，需要一种更安全的方法来提供这种治疗。我们已经发现雌激素增加了血管功能障碍的主要介质--肾素-血管紧张素-醛固酮系统的活性，这种增加与肾血流量的下降有关。我们还发现雌激素增加血管损伤和盐皮质激素受体的mRNA。我们假设屈螺酮（一种具有与孕酮相似的抗盐皮质激素活性的雌激素）与雌激素联合给药可减少传统激素替代（雌激素+甲羟孕酮）的不良血管效应。2)确定糖尿病预防计划（DPP）是否可以转化为有妊娠糖尿病（GDM）病史的女性的社区环境，以降低进展为2型糖尿病（T2 DM）的风险。2型糖尿病是心血管疾病的主要危险因素，尤其是在女性中。既往患有GDM的女性进展为T2 DM的风险较高。DPP表明，改变生活方式可以降低T2 DM的风险。我们假设，修改后的DPP交付在社区环境中将有效地减少产后体重保持在近期GDM的妇女。

DESCRIPTION (provided by applicant): This project has as its goal the mentoring of junior investigators in patient-oriented research through my research program in unique cardiovascular risk factors in women. Mentoring Goal: To maintain my mentoring program in patient-oriented research, continue to increase the number of women and minorities who enter this field and allow my program to further develop within the Harvard CTSA. The K24 will enable me to achieve these goals by allowing me to maintain the decrease in clinical care and administrative time that I achieved with the original K 24 award. Research Projects: This application is based on two translational research projects: 1) The determination of whether a progestin with antimineralocorticoid activity can ameliorate or prevent estrogen-induced cardiovascular complications in postmenopausal women. For many postmenopausal women, vasomotor symptoms are a major cause of decreased quality of life. Estrogen is the only FDA approved treatment for these symptoms. Recent studies have shown that estrogen increases risk for cardiovascular disease (CVD). Therefore, a safer way to provide such therapy is in need. We have shown that estrogen increases renin-angiotensin-aldosterone system activity, a major mediator of vascular dysfunction and that this increase is associated with a fall in renal blood flow. We have also shown that estrogen increases vascular damage and mRNA for the mineralocorticoid receptor. We postulate that drospirenone, a progestin, with antimineralocorticoid activity similar to progesterone, given with estrogen will decrease adverse vascular effects of traditional hormone replacement (estrogen + medroxyprogesterone). 2) The determination of whether the Diabetes Prevention Program (DPP) can be translated into the community setting for women with a history of gestational diabetes (GDM) to reduce the risk of progression to Type 2 diabetes (T2DM). T2DM is a major risk factor for CVD, particularly in women. Women with prior GDM have a high risk of progression to T2DM. The DPP demonstrated that lifestyle modification can decrease the risk for T2DM. We postulate that a modified DPP delivered in a community setting will be effective in decreasing postpartum weight retention in women with recent GDM.