AGE DEPENDENT REGULATION OF HEMOSTASIS
年龄依赖性止血调节
基本信息
- 批准号:6011569
- 负责人:
- 金额:$ 33.28万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-07-01 至 2003-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION: (Adapted from investigator's abstract) Blood coagulation activity
in the normal human population elevates with advancing age. When combined with
age-dependent disorders like atherosclerosis, this increase in the coagulation
potential may play a role in the increased frequency of cardiovascular and
thrombotic disorders in the elderly. Presently, little is known about the
molecular mechanisms responsible for this phenomenon and homeostasis of the
coagulation system in general. The long-term goal of this proposal is to
determine the molecular mechanisms underlying age-dependent regulation and
homeostasis of the blood coagulation system. The factor IX gene will serve as
an initial model gene for intensive studies. Recently the applicant has
identified two major activities associated with specific regions of the factor
IX gene that are essential for age-dependent regulation of expression. This
proposal has five specific aims. Specific Aim 1 is to establish the mechanisms
of action of two cis-acting elements, AE5' (a PEA3 binding element) and AE3' (a
sequence containing extensive dinucleotide repeats) in age-dependent regulation
of the human factor IX gene. Specific Aim 2 is to delineate the switch
mechanisms in expression of transcriptional factors over the puberty period.
Specific Aim 3 is to identify potential additional gene structures with
modifying activities on age-dependent regulation of the gene. Specific Aim 4 is
to determine the physiological significance of advancing age-dependent
elevation in factor IX gene expression by constructing a mouse model lacking
such elevation in the endogenous mouse factor IX gene. Specific Aim 5 is to
determine the biological significance of elevated or lowered plasma factor IX
levels in relation to age. The molecular mechanisms established for the factor
IX gene will facilitate subsequent studies on other key coagulation factors and
regulators, laying the foundation for comprehensive understanding of the
overall age-dependent regulation (homeostasis) of the coagulation system. Such
knowledge may help develop novel and/or improved treatments for hemorrhagic
disorders as well as thrombotic and cardiovascular diseases in the elderly.
描述:(改编自研究者摘要)血液凝固活性
项目成果
期刊论文数量(0)
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KOTOKU KURACHI其他文献
KOTOKU KURACHI的其他文献
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