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Targeting microRNA-33 to reduce intracranial atherosclerosis and other neurovascular hallmarks of vascular cognitive impairment and dementia

Targeting microRNA-33 to reduce intracranial atherosclerosis and other neurovascular hallmarks of vascular cognitive impairment and dementia
靶向 microRNA-33 减少颅内动脉粥样硬化以及血管性认知障碍和痴呆的其他神经血管标志
批准号:
9765860
负责人:
Ryan Eugene Temel
金额:
$42.08万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-04-01 至 2022-03-31

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中文摘要
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英文摘要
Project Summary Intracranial atherosclerosis (ICAS) is a public health concern for both its role in stroke and as a contributing factor to vascular cognitive impairment and dementia (VCID). It is becoming widely accepted that poor vascular health facilitates poor brain health and that changes are needed to delay or prevent onset of VCID. Atherosclerotic vascular disease (AVD) is a chronic, maladaptive inflammatory disease that can affect extra- and intracranial arteries. The combination of lipoprotein retention, endothelial cell inflammation, monocyte/macrophage infiltration, intracellular cholesterol accumulation, impaired apoptotic cell clearance, and extracellular matrix degradation leads to formation of advanced, unstable atherosclerotic plaques that can limit or occlude blood flow to tissues causing acute or chronic tissue damage. ICAS often plays a causative role in ischemic stroke and subsequent cognitive decline. ICAS has also been linked to both clinical signs of cognitive decline and Alzheimer's disease pathology. Intracranial compared to extracranial atherosclerosis has a delayed onset of ~20 years but increases in prevalence and severity in individuals 60 years or older. With the steady rise in the percentage of US citizens above the age of 60, ICAS will play an ever-growing role in the morbidity and mortality caused by VCID. Reducing low-density lipoprotein (LDL) concentration with statins is a primary therapeutic approach to stabilize AVD and attenuate ischemic stroke risk. However, statins only reduce stroke risk by ~20% and do not appear to reduce VCID suggesting that treating hypercholesterolemia alone is not an ideal approach for reducing VCID. The obvious need for additional therapies that regress or stabilize ICAS has been hampered by the paucity of suitable animal models. During an R01-funded study to determine the impact of microRNA-33 (miR-33) antagonism on cardiovascular AVD, we fortuitously discovered that our NHP model had ICAS and other neurovascular hallmarks of VCID. We believe analysis of intracranial arteries and brains from our NHPs could have a high impact on the field of VCID research because of the potential discovery of a new therapy and animal model for VCID.
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Effects of Anti-miR-33 on Atherosclerosis Regression and RCT in Nonhuman Primates
Effects of Anti-miR-33 on Atherosclerosis Regression and RCT in Nonhuman Primates
  • 批准号:
    8968259
  • 项目类别:
  • 资助金额:
    $71.39万
  • 财政年份:
    2013
  • 负责人:
    Ryan Eugene Temel
  • 依托单位:
Effects of Anti-miR-33 on Atherosclerosis Regression and RCT in Nonhuman Primates
  • 批准号:
    8774254
  • 项目类别:
  • 资助金额:
    $72.5万
  • 财政年份:
    2013
  • 负责人:
    Ryan Eugene Temel
  • 依托单位:
Effects of Anti-miR-33 on Atherosclerosis Regression and RCT in Nonhuman Primates
  • 批准号:
    9352511
  • 项目类别:
  • 资助金额:
    $5.4万
  • 财政年份:
    2013
  • 负责人:
    Ryan Eugene Temel
  • 依托单位:
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