Vascular Remodeling in Overweight and Obese Adolescents

超重和肥胖青少年的血管重塑

• 批准号: 8522220
• 负责人: Justin P.V. Zachariah
• 金额: $ 13.97万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-06 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8522220
• 关键词: 18 year old; Adolescent; Adult; Age; Age-Years; Aldosterone; Arteries; Attenuated; Award; Biochemical; Biological; Biological Markers; Blood Pressure; Blood Vessels; Body Weight decreased; Body mass index; C-reactive protein; Caliber; Camping; Cardiology; Cardiovascular Diseases; Cardiovascular system; Characteristics; Child; Childhood; Cholesterol; Clinical; Clinical Trials; Coronary heart disease; Country; Data; Diabetes Mellitus; Disease; Echocardiography; Event; Funding; Future; Glucose; Hypertension; Inflammation; Insulin; Insulin Resistance; Intake; Intervention; Isolated systolic hypertension; Leptin; Leptin resistance; Link; Measures; Mechanics; Mediating; Mediator of activation protein; Medical; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentorship; Obesity; Overweight; Pathway interactions; Patients; Peripheral Resistance; Phenotype; Physiologic pulse; Positioning Attribute; Prevalence; Pulse Pressure; Quality of life; Renin; Research; Research Personnel; Research Project Grants; Research Technics; Resources; Risk; Risk Factors; Role; Stratification; Structure; System; Testing; Time; Training; Translational Research; United States National Institutes of Health; Variant; Vascular remodeling; Weight; Work; arterial stiffness; cardiovascular disorder risk; catalyst; cost effectiveness; electric impedance; hemodynamics; high risk; improved; indexing; mortality; secondary outcome; tonometry

DESCRIPTION (provided by applicant): Large-artery vascular remodeling, such as arterial stiffening and dilation, is a biophysical antecedent to hypertension in adults. Emerging data in children identifies vascular remodeling as a feature of obesity, which is associated with present and future hypertension. Dr. Zachariah's research project examines the central hypothesis that excess weight in adolescents is related to vascular remodeling by assessing cross-sectional correlation as well as longitudinal change after weight loss. Using a combined tonometry-echocardiography system, Specific Aim 1 explores the hypothesis that excess weight will be associated with higher conduit arterial stiffness as indexed by central pulse pressure (PP), forward pulse wave (FPW), characteristic impedance (Zc) and carotid femoral pulse wave velocity (CFPWV), as well as with arterial dilation as indexed by larger effective aortic diameter (Da). Peripheral resistance (Zo) will be lower leading to higher pulse wave reflection as indexed by global reflection coefficient (RC). Secondary hypotheses include that a) the majority of the variation in central PP will be due to FPW, and b) the association between excess weight and vascular remodeling will be attenuated by circulating markers of insulin resistance, leptin resistance, inflammation, and aldosterone-to-renin ratio. Specific Aim 2 examines the effect of 2 months of weight loss on arterial stiffness and pulsatile load in 54 excess weight adolescents 13-18 attending a summer weight loss camp The educational component of this K23 award will include hands-on training in vascular testing and didactic course- work in analysis of biomarkers, analysis of multiple biomarker "-omic" platforms, and clinical trials. Mentorship will come from Drs. Jane Newburger, Vasan Ramachandran, and Gary Mitchell who have specific expertise in pediatric cardiovascular disease (CVD), adult CVD, circulating biomarkers in CVD, and vascular phenotypes in CVD. Enhanced by support from the NIH-sponsored Harvard Catalyst Clinical Translational Science Unit and the Department of Cardiology, the proposed K23 award will provide structured mentorship, protected research time, and training in modular, broadly applicable cardiovascular research techniques. The award will position Dr. Zachariah to be one of the few independently-funded pediatric cardiology clinical researchers in the country studying vascular medicine in high-risk children.

描述（由申请人提供）：大动脉血管重塑，例如动脉僵硬和扩张，是成年人高血压的生物物理前期。儿童的新兴数据将血管重塑视为肥胖症的特征，这与当前和未来的高血压有关。 Zachariah博士的研究项目研究了一个中心假设，即青少年的过量体重通过评估横截面相关性以及体重减轻后的纵向变化而与血管重塑有关。 Using a combined tonometry-echocardiography system, Specific Aim 1 explores the hypothesis that excess weight will be associated with higher conduit arterial stiffness as indexed by central pulse pressure (PP), forward pulse wave (FPW), characteristic impedance (Zc) and carotid femoral pulse wave velocity (CFPWV), as well as with arterial dilation as indexed by larger effective aortic diameter (Da).外围电阻（ZO）将较低，从而导致较高的脉搏波反射，如全局反射系数（RC）所索引。次要假设包括a）a）中央PP的大部分变化将是由于FPW引起的，b）b）重量过多与血管重塑之间的关联将通过胰岛素抵抗，瘦素耐药性，炎症，炎症和醛固酮与肾蛋白蛋白比率的循环标记来减弱。 Specific Aim 2 examines the effect of 2 months of weight loss on arterial stiffness and pulsatile load in 54 excess weight adolescents 13-18 attending a summer weight loss camp The educational component of this K23 award will include hands-on training in vascular testing and didactic course- work in analysis of biomarkers, analysis of multiple biomarker "-omic" platforms, and clinical trials.指导将来自博士。 Jane Newburger，Vasan Ramachandran和Gary Mitchell在儿科心血管疾病（CVD），成人CVD，CVD中循环生物标志物和CVD中具有血管表型。通过NIH赞助的哈佛催化剂临床转化科学部门和心脏病学系的支持增强，拟议的K23 Award将提供结构化指导，受保护的研究时间和模块化，广泛适用的心血管研究技术的培训。该奖项将使Zachariah博士成为该国少数独立资助的儿科心脏病学研究人员之一，该研究人员正在研究高危儿童的血管医学。