Project 4 - Cardiovascular domain

项目4-心血管领域

• 批准号: 8663297
• 负责人: Hao Mei
• 金额: $ 29.45万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8663297
• 关键词: 3' Flanking Region; Accounting; Age; Aging; Alcohol consumption; Arteries; Biological Aging; Biological Markers; Blood Flow Velocity; Blood Vessels; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Childhood; Chromosomes; Clinical; Complement; Data; Elderly; Event; Exons; Exposure to; Genes; Genetic; Genetic Determinism; Genetic Predisposition to Disease; Genomics; Genotype; Grouping; Haplotypes; Heart; Heritability; Impairment; Indium; Individual; Instruction; Length; Leukocytes; Life; Link; Literature; Louisiana; Measures; Mentors; Methods; Natural regeneration; Nonagenarian; Obesity; Participant; Phenotype; Physiologic pulse; Population Growth; Public Health; Publishing; Pulse Pressure; RNA Splicing; Regenerative Medicine; Research; Sampling; Sampling Studies; Scanning; Signal Transduction; Site; Stem cells; Structure; Testing; Thick; Time; Tobacco smoke; Variant; Vascular remodeling; age related; cohort; early childhood; follow-up; genetic association; genetic variant; genome-wide linkage; healthy aging; human old age (65+); indexing; intima media; lifestyle factors; mortality; non-genetic; population based; prevent; rare variant; telomere

Vascular aging (VA) is the progressive vascular remodeling and alteration of vascular structure that accompanies biological aging. VA results in an increase in artery stiffness, accompanied by impairment of endothelial regeneration and shortening of leukocyte telomere length (LTL). The progress of VA in early age strongly predicts the occurrence of CVD, the leading cause of death in old age. This progress is determined in part by genetic factors, with effects modifiable by exposure to various non-genetic factors. The overall objective of this proposal is to identify genetic components with modest-to-large longitudinal effects on the progress of VA from childhood, and to investigate the association of genetic components with circulating endothelial progenitor cells (EPCs) and leukocyte telomere length (LTL) that represent endothelial regeneration and biological aging respectively. Our specific aims are to: (1) Identify genomic linkage regions and candidate genes underlying VA. The hypotheses are that one or more chromosome regions exert modest-to-large, heritable genetic effects on VA phenotypes from early childhood, and that some candidate genes exert modest-to-large effects but lack detectable heritability. (2) Determine common and rare effect variants at the genomic linkage regions and candidate genes identified in Specific Aim 1 that are associated with VA, endothelial regeneration and biological aging. The hypotheses are that genetic determinants underlying VA phenotypes are related to circulating EPCs and LTL, and rare functional variants in five important candidate genes are associated with longitudinal VA phenotypes in the upper and lower 5% of BHS participants. (3) Validate significant findings from Specific Aim 2 in a replication sample. The hypothesis is that the findings of common and rare effect variants will be repeated in a random populationbased sample and are associated with healthy aging. It is expected that identification of effect variants underlying VA will be important for defining genetic predisposition to vascular aging or healthy aging later in life.

血管老化（Vascular aging， VA）是一种渐进的血管重构和血管结构改变的过程