GDM Effect on Maternal/Neonatal Endothelial Progenitors

GDM 对母体/新生儿内皮祖细胞的影响

• 批准号: 7233320
• 负责人: Laura S Haneline
• 金额: $ 18.94万
• 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/7233320
• 关键词: angiogenesis; blood glucose; cardiovascular disorder risk; cell population study; cellular pathology; clinical research; cord blood; diabetes mellitus therapy; diet therapy; gestational diabetes mellitus; hematopoietic stem cells; human pregnant subject; hyperglycemia; mother /embryo /fetus nutrition; newborn human (0-6 weeks); noninsulin dependent diabetes mellitus; pathologic process; pregnancy circulation; prenatal care; vascular endothelium

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）：妊娠糖尿病（GDM）很常见，大约有4％的怀孕。大部分GDM女性在10年内发展出II型DM。此外，具有GDM史的非怀孕妇女表现出血管功能障碍。重要的是，与DM相关的血管疾病对这种慢性疾病的病态和死亡率有显着贡献。但是，DM导致血管疾病的机制尚不清楚。此外，新兴的证据表明，糖尿病内环境增加了后代发展慢性成人疾病的风险，包括II型DM，代谢综合征和高血压。总的来说，这些观察构成了我们整体假设的基础。我们假设胎儿​​暴露于糖尿病内环境会加速血管功能障碍的发作，并增加成人血管疾病的风险。血管健康的关键成分是对受损的内皮的有效修复以及通过内皮祖细胞（EPC）形成新血管的能力。然而，评估高血糖对EPC功能的影响的主要研究的主要局限性是未能使用定义其他干/祖细胞群体来识别EPC，包括高度增殖性质，自我更新能力和在体内从头开始组成。我们计划检查高血糖对先前证明的两个细胞群体的影响：CFU-ECS，血管生成造血细胞和ECFC（一种内皮祖细胞群体）。在特定的目标1中，我们将研究高血糖对从正常的完整交付中获得的脐带血CFU-EC和ECFC的影响。在特定的目标2中，我们将评估患有GDM的母亲的婴儿是否表现出CFU-EC和ECFC功能降低以及血管反应性的改变。最后，我们将检查产妇血糖控制是否与母体和婴儿CFU-EC和ECFC功能相关。了解母体DM在其后代中引起血管疾病的机制可能会阐明潜在的预防策略，并为治疗这些人提供进步。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子或生物标志物的潜力，以便可以实施早期干预措施以破坏或扭转这一过程并影响不断升级的医疗保健问题。摘要摘要：患有妊娠糖尿病的母亲出生的婴儿患成人疾病的风险增加，包括血管疾病。我们将测试患有妊娠糖尿病的母亲出生的婴儿是否具有修复并制造新血管的细胞功能异常。