GDM Effect on Maternal and Neonatal Endothelial Progenitors and Vascular Function

GDM 对孕产妇和新生儿内皮祖细胞和血管功能的影响

• 批准号: 7295819
• 负责人: Laura S Haneline
• 金额: $ 21.4万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-25 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7295819
• 关键词: Activities of Daily Living; Acute; Adult; Antigens; Biological Markers; Blood Vessels; Cell physiology; Cells; Characteristics; Child; Chronic; Chronic Disease; Data; Development; Diabetic intrauterine environment; Disease; Early Intervention; Endothelial Cells; Endothelium; Exhibits; Exposure to; Failure; Fetus; Functional disorder; Gestational Diabetes; Health; Healthcare; Hematopoietic; Hyperglycemia; Hypertension; In Vitro; Individual; Infant; Lead; Maintenance; Metabolic syndrome; Morbidity - disease rate; Mothers; Nature; Neonatal; Numbers; Patients; Perinatal; Perinatal Exposure; Population; Pregnancy; Prevention strategy; Process; Range; Recording of previous events; Research Personnel; Risk; Stem cells; Stress; Testing; Umbilical Cord Blood; Vascular Diseases; Woman; angiogenesis; base; disorder risk; fetal; glycemic control; in utero; in vivo; mortality; neonatal morbidity; neonate; novel; peripheral blood; progenitor; programs; repaired; self-renewal; stem

DESCRIPTION (provided by applicant): Gestational diabetes (GDM) is common, occurring in approximately 4% of all pregnancies. A large proportion of women with GDM develop Type II DM within 10 years. In addition, nonpregnant women with a prior history of GDM exhibit vascular dysfunction. Importantly, vascular diseases associated with DM contribute significantly to the morbidities and mortality of this chronic disease. However, the mechanism by which DM leads to vascular disease is unknown. Furthermore, emerging evidence suggest that the diabetic intrauterine environment increases the risk for offspring to develop chronic adult diseases including Type II DM, the metabolic syndrome, and hypertension. Collectively, these observations form the basis for our overall hypothesis. We hypothesize that fetal exposure to a diabetic intrauterine environment accelerates the onset of vascular dysfunction and increases the risk for the development of adult vascular disease. A critical component of vascular health is efficient repair of damaged endothelium and ability to form new blood vessels by endothelial progenitor cells (EPCs). However, a major limitation to previous studies assessing the effect of hyperglycemia on EPC function was the failure to identify EPCs using principals that define other stem/progenitor cell populations including highly proliferative nature, self-renewal capacity, and de novo vessel formation in vivo. We plan to examine the effect of hyperglycemia on two cell populations previously shown to contribute to angiogenesis: CFU-ECs, angiogenic hematopoietic cells, and ECFCs, an endothelial progenitor population. In Specific Aim 1, we will examine the effect of hyperglycemia on cord blood CFU-ECs and ECFCs obtained from normal full-term deliveries. In Specific Aim 2, we will evaluate whether infants of mothers with GDM exhibit diminished CFU-EC and ECFC function as well as altered vascular reactivity. Finally, we will examine whether maternal glycemic control correlates with maternal and infant CFU-EC and ECFC function. Understanding the mechanism(s) by which maternal DM elicits vascular disease in her offspring will likely elucidate potential prevention strategies as well as provide advances in the treatment of these individuals. Furthermore, studies in neonates and infants offer the potential to identify early predictors or biomarkers of adult disease risk such that early intervention may be implemented to disrupt or reverse this process and impact an escalating health care problem. Lay summary: Infants born to mothers with gestational diabetes are at increased risk to develop adult diseases, including diseases of the blood vessels. We will test whether infants born to mothers with gestational diabetes have abnormal function of cells that repair and make new blood vessels.

描述（由申请人提供）：妊娠期糖尿病 (GDM) 很常见，约占所有妊娠的 4%。很大一部分患有 GDM 的女性在 10 年内发展为 II 型糖尿病。此外，有 GDM 病史的非孕妇表现出血管功能障碍。重要的是，与糖尿病相关的血管疾病对这种慢性疾病的发病率和死亡率有很大影响。然而，DM 导致血管疾病的机制尚不清楚。此外，新出现的证据表明，糖尿病宫内环境会增加后代患慢性成人疾病的风险，包括 II 型糖尿病、代谢综合征和高血压。总的来说，这些观察结果构成了我们总体假设的基础。我们假设胎儿​​暴露于糖尿病宫内环境会加速血管功能障碍的发生并增加成人血管疾病的风险。血管健康的一个重要组成部分是有效修复受损内皮以及内皮祖细胞 (EPC) 形成新血管的能力。然而，先前评估高血糖对 EPC 功能影响的研究的一个主要限制是未能使用定义其他干细胞/祖细胞群的原理（包括高度增殖性、自我更新能力和体内从头血管形成）来识别 EPC。我们计划检查高血糖对先前显示有助于血管生成的两个细胞群的影响：CFU-EC（血管生成造血细胞）和 ECFC（内皮祖细胞群）。在具体目标 1 中，我们将检查高血糖对正常足月分娩的脐带血 CFU-EC 和 ECFC 的影响。在具体目标 2 中，我们将评估患有 GDM 的母亲所生的婴儿是否表现出 CFU-EC 和 ECFC 功能降低以及血管反应性改变。最后，我们将检查母亲血糖控制是否与母亲和婴儿 CFU-EC 和 ECFC 功能相关。了解母亲糖尿病引起后代血管疾病的机制可能会阐明潜在的预防策略，并为这些个体的治疗提供进展。此外，对新生儿和婴儿的研究提供了识别成人疾病风险的早期预测因素或生物标志物的潜力，以便可以实施早期干预来破坏或逆转这一过程并影响不断升级的医疗保健问题。简单总结：患有妊娠糖尿病的母亲所生的婴儿患成人疾病（包括血管疾病）的风险增加。我们将测试患有妊娠糖尿病的母亲所生的婴儿是否具有修复和制造新血管的细胞功能异常。