PREVENTION OF VASCULOPATHY AND NEPHROPATHY IN METABOLIC SYNDROME

预防代谢综合征中的血管病变和肾病

基本信息

  • 批准号:
    7341755
  • 负责人:
  • 金额:
    $ 28.76万
  • 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:
    1999-01-01 至 2011-01-31
  • 项目状态:
    已结题

项目摘要

Accelerated atherosclerosis and premature aging of the cardiovascular system in patients with diabetes mellitus and metabolic syndrome have acquired epidemic proportions. Our previous studies of endothelial cells subjected to a microenvironment emulating the diabetic milieu revealed accelerated development of cell senescence. Based on the observations that the expression of nitrotyrosine-modified proteins was enhanced in the prematurely senescent cells and peroxynitrite treatment of intact cells led to premature senescence, we treated endothelial cells with a bona fide peroxynitrite scavenger/antioxidant ebselen. Such a treatment was associated with the prevention and reversal of premature senescence. These findings prompted us to investigate the molecular mechanism(s) of premature cell senescence, effects of ebselen on premature endothelial cell senescence in a model of metabolic syndrome - Zucker diabetic rats, and examine the development of vasculopathy in these animals. We hypothesize that oxidative stress/peroxynitrite-induced lysosomal dysfunction initiates endothelial cell senescence and accumulation of gangliosides, a molecular switch from senescence to apoptosis- events underpinning the progression of vasculopathy. In vitro and in vivo studies employing image analysis and fluorescence intravital microscopy, biochemical techniques to detect leakage of lysosomal and mitochondria! proteins as well as accumulation of gangliosides, and quntitative analysis of the markers of cell cycle are designed to investigate molecular and cellular mechanisms of premature senescence and apoptosis. In vivo studies of the Zucker diabetic fat rat treated with ebselen will be conducted to examine the possibility of preventing and reversing macro- and micro-vasculopathy (nephropathy) in this syndrome. The investigations may shed light on mechanisms of premature senescence of endothelial cells, role of peroxynitrite in initiating it, and potential therapeutic efficacy of peroxynitrite scavenging in amelioration of vasculopathy.
糖尿病患者心血管系统加速动脉粥样硬化和早衰

项目成果

期刊论文数量(0)
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会议论文数量(0)
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MICHAEL S GOLIGORSKY其他文献

MICHAEL S GOLIGORSKY的其他文献

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{{ truncateString('MICHAEL S GOLIGORSKY', 18)}}的其他基金

Glycocalyx repair in sepsis using liposomal carriers of preassembled glycocalyx
使用预组装糖萼的脂质体载体修复脓毒症中的糖萼
  • 批准号:
    10428550
  • 财政年份:
    2019
  • 资助金额:
    $ 28.76万
  • 项目类别:
Glycocalyx repair in sepsis using liposomal carriers of preassembled glycocalyx
使用预组装糖萼的脂质体载体修复脓毒症中的糖萼
  • 批准号:
    10218261
  • 财政年份:
    2019
  • 资助金额:
    $ 28.76万
  • 项目类别:
ENDOTHELIAL DYSFUNCTION, NITRIC OXIDE AND RENAL FAILURE
内皮功能障碍、一氧化氮和肾衰竭
  • 批准号:
    7990202
  • 财政年份:
    2009
  • 资助金额:
    $ 28.76万
  • 项目类别:
Weibel - Palade Bodies - Sentinels of Acute Ischemia
Weibel - Palade Bodies - 急性缺血的哨兵
  • 批准号:
    7921552
  • 财政年份:
    2009
  • 资助金额:
    $ 28.76万
  • 项目类别:
PREVENTION OF VASCULOPATHY AND NEPHROPATHY IN METABOLIC SYNDROME
预防代谢综合征中的血管病变和肾病
  • 批准号:
    7990210
  • 财政年份:
    2009
  • 资助金额:
    $ 28.76万
  • 项目类别:
Weibel - Palade Bodies - Sentinels of Acute Ischemia
Weibel - Palade Bodies - 急性缺血的哨兵
  • 批准号:
    8298636
  • 财政年份:
    2009
  • 资助金额:
    $ 28.76万
  • 项目类别:
Weibel - Palade Bodies - Sentinels of Acute Ischemia
Weibel - Palade Bodies - 急性缺血的哨兵
  • 批准号:
    8496014
  • 财政年份:
    2009
  • 资助金额:
    $ 28.76万
  • 项目类别:
Weibel - Palade Bodies - Sentinels of Acute Ischemia
Weibel - Palade Bodies - 急性缺血的哨兵
  • 批准号:
    7700338
  • 财政年份:
    2009
  • 资助金额:
    $ 28.76万
  • 项目类别:
Weibel - Palade Bodies - Sentinels of Acute Ischemia
Weibel - Palade Bodies - 急性缺血的哨兵
  • 批准号:
    8079698
  • 财政年份:
    2009
  • 资助金额:
    $ 28.76万
  • 项目类别:
VASCULAR PERMEABILITY IN DIABETIC NEPHROPATHY
糖尿病肾病的血管通透性
  • 批准号:
    6342524
  • 财政年份:
    1999
  • 资助金额:
    $ 28.76万
  • 项目类别:

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  • 批准号:
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  • 财政年份:
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    $ 28.76万
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GLOMERULAR EFFECTS OF ADVANCED GLYCOSYLATION END PRODUCTS
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