Role of bioactive lipids in the protective pathways of obesity in ischemic cardi

生物活性脂质在缺血性心脏病肥胖保护途径中的作用

基本信息

  • 批准号:
    9135493
  • 负责人:
  • 金额:
    $ 25.59万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
  • 资助国家:
    美国
  • 起止时间:
  • 项目状态:
    未结题

项目摘要

Obesity is approaching epidemic state in the western worid and is a known risk factor for acute myocardial infarction (AMI). AMI and the subsequent ischemic heart disease (IHD) are often complicated with high mortality and poor overall prognosis despite significant advances in medical therapy and revascularization strategies. Currently, short of heart transplantation with all of its inherit limitations, there are no available treatment strategies that replace the infracted myocardium and therapies are largely palliative. Paradoxically, obesity may also confer a protective effect against AMI-associated remodeling which leads to IHD. The molecular kiasis for this protection is poorly understood. AMI initiates poorly understood innate reparatory mechanisms through which BMSPCs are mobilized and home towards the ischemic myocardium contributing to myocardial regeneration and correlating with cardiac recovery. Our preliminary data indicates that bioactive lipids such as sphingosine-1 phosphate (SIP), but not traditional chemokines, play a quintessential role in this mobilization and homing. Interestingly, obesity and the associated metabolic syndrome are associated with alterations in bioactive lipids' metabolism. Our objective in this application, therefore, is to develop better understanding ofthe obesity-associated alterations in AMI-induced stem cell mobilization pathways, specially those involving bioactive lipids, and devise therapies that hamess this process for therapeutic myocardial regeneration strategies. Our central hypothesis has been formulated based upon the existing literature and our strong preliminary data demonstrating that BMSPCs express SIP receptors and will migrate towards plasma from AMI patients in an SI P dependent fashion. Our rationale for these studies is that understanding the protective role of bioactive lipids and stem cell mobilization during AMI in obesity would help establish a strong scientific framework for eventual generalizable human myocardial regenerative clinical trials utilizing the available and new pharmacological modulators of bioactive lipids and their receptors. In addition to clinical studies, our approach will exploit small molecule-strategies in mouse models through examining the obesity associated molecular and cellular pathways, specially those involving bioactive lipids, that are activated by myocardial infarction (Aim 1); and examine the modulation of bioactive lipids' metabolism and receptor expression to enhance cardiac recovery following AMI (Aim 2).
肥胖在西方世界已接近流行状态,是急性心肌梗死的已知危险因素。 心肌梗死(AMI)。AMI和随后的缺血性心脏病(IHD)通常并发高血压, 尽管药物治疗和血运重建取得了显着进展,但死亡率和总体预后仍较差 战略布局目前,由于心脏移植的遗传局限性, 替代梗死心肌的治疗策略和疗法主要是姑息性的。巧合的是, 肥胖也可赋予对导致IHD的AMI相关重塑的保护作用。的 对这种保护作用的分子基础知之甚少。急性心肌梗死引发了人们知之甚少的先天性修复 BMSPC被动员并向缺血心肌归巢的机制 有助于心肌再生并与心脏恢复相关。我们的初步数据显示 生物活性脂质,如鞘氨醇-1磷酸(SIP),而不是传统的趋化因子, 在这场动员和归巢中扮演着典型的角色。有趣的是,肥胖和相关的代谢 综合征与生物活性脂质代谢的改变有关。我们申请的目的, 因此,更好地理解肥胖相关的AMI诱导的干细胞改变, 动员途径,特别是那些涉及生物活性脂质,并设计治疗, 治疗性心肌再生策略的方法。我们的核心假设已经被明确表述为 基于现有的文献和我们强有力的初步数据表明,BMSPC表达SIP 受体,并将以SIP依赖性方式从AMI患者向血浆迁移。我们的理由是 这些研究是,了解生物活性脂质和干细胞动员的保护作用, AMI在肥胖中的应用将有助于建立一个强有力的科学框架, 心肌再生的临床试验利用现有的和新的药理学调节剂的生物活性 脂质及其受体。除了临床研究,我们的方法将利用小分子策略, 通过检查肥胖相关的分子和细胞途径,特别是那些 涉及由心肌梗死激活的生物活性脂质(目的1);并检查 生物活性脂质的代谢和受体表达促进AMI后心脏恢复(目的2)。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Ahmed Abdel-Latif其他文献

Ahmed Abdel-Latif的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Ahmed Abdel-Latif', 18)}}的其他基金

Lysophosphatidic Acid Mediates Cardiac Inflammation After Acute Infarction
溶血磷脂酸介导急性梗塞后的心脏炎症
  • 批准号:
    9977877
  • 财政年份:
    2017
  • 资助金额:
    $ 25.59万
  • 项目类别:
Lysophosphatidic Acid Mediates Cardiac Inflammation After Acute Infarction
溶血磷脂酸介导急性梗塞后的心脏炎症
  • 批准号:
    10698647
  • 财政年份:
    2017
  • 资助金额:
    $ 25.59万
  • 项目类别:
Lysophosphatidic Acid Mediates Cardiac Inflammation After Acute Infarction
溶血磷脂酸介导急性梗塞后的心脏炎症
  • 批准号:
    10213118
  • 财政年份:
    2017
  • 资助金额:
    $ 25.59万
  • 项目类别:
Lysophosphatidic Acid Mediates Cardiac Inflammation After Acute Infarction
溶血磷脂酸介导急性梗塞后的心脏炎症
  • 批准号:
    9367360
  • 财政年份:
    2017
  • 资助金额:
    $ 25.59万
  • 项目类别:
Lysophosphatidic Acid Mediates Cardiac Inflammation After Acute Infarction
溶血磷脂酸介导急性梗塞后的心脏炎症
  • 批准号:
    9753340
  • 财政年份:
    2017
  • 资助金额:
    $ 25.59万
  • 项目类别:
Role of Bioactive Lipids in Stem Cell Mobilization and Homing in Cardiac Ischemia
生物活性脂质在心脏缺血干细胞动员和归巢中的作用
  • 批准号:
    8903528
  • 财政年份:
    2014
  • 资助金额:
    $ 25.59万
  • 项目类别:
Role of bioactive lipids in the protective pathways of obesity in ischemic cardi
生物活性脂质在缺血性心脏病肥胖保护途径中的作用
  • 批准号:
    8733727
  • 财政年份:
  • 资助金额:
    $ 25.59万
  • 项目类别:
Role of bioactive lipids in the protective pathways of obesity in ischemic cardi
生物活性脂质在缺血性心脏病肥胖保护途径中的作用
  • 批准号:
    8602578
  • 财政年份:
  • 资助金额:
    $ 25.59万
  • 项目类别:

相似海外基金

Deciphering the role of adipose tissue in common metabolic disease via adipose tissue proteomics
通过脂肪组织蛋白质组学解读脂肪组织在常见代谢疾病中的作用
  • 批准号:
    MR/Y013891/1
  • 财政年份:
    2024
  • 资助金额:
    $ 25.59万
  • 项目类别:
    Research Grant
ESTABLISHING THE ROLE OF ADIPOSE TISSUE INFLAMMATION IN THE REGULATION OF MUSCLE MASS IN OLDER PEOPLE
确定脂肪组织炎症在老年人肌肉质量调节中的作用
  • 批准号:
    BB/Y006542/1
  • 财政年份:
    2024
  • 资助金额:
    $ 25.59万
  • 项目类别:
    Research Grant
Canadian Alliance of Healthy Hearts and Minds: Dissecting the Pathways Linking Ectopic Adipose Tissue to Cognitive Dysfunction
加拿大健康心灵联盟:剖析异位脂肪组织与认知功能障碍之间的联系途径
  • 批准号:
    479570
  • 财政年份:
    2023
  • 资助金额:
    $ 25.59万
  • 项目类别:
    Operating Grants
Determinants of Longitudinal Progression of Adipose Tissue Inflammation in Individuals at High-Risk for Type 2 Diabetes: Novel Insights from Metabolomic Profiling
2 型糖尿病高危个体脂肪组织炎症纵向进展的决定因素:代谢组学分析的新见解
  • 批准号:
    488898
  • 财政年份:
    2023
  • 资助金额:
    $ 25.59万
  • 项目类别:
    Operating Grants
Activation of human brown adipose tissue using food ingredients that enhance the bioavailability of nitric oxide
使用增强一氧化氮生物利用度的食品成分激活人体棕色脂肪组织
  • 批准号:
    23H03323
  • 财政年份:
    2023
  • 资助金额:
    $ 25.59万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of new lung regeneration therapies by elucidating the lung regeneration mechanism of adipose tissue-derived stem cells
通过阐明脂肪组织干细胞的肺再生机制开发新的肺再生疗法
  • 批准号:
    23K08293
  • 财政年份:
    2023
  • 资助金额:
    $ 25.59万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A study on the role of brown adipose tissue in the development and maintenance of skeletal muscles
棕色脂肪组织在骨骼肌发育和维持中作用的研究
  • 批准号:
    23K19922
  • 财政年份:
    2023
  • 资助金额:
    $ 25.59万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
Adipose Tissue T Cell Polarization and Metabolic Health in Persons Living with HIV
HIV 感染者的脂肪组织 T 细胞极化和代谢健康
  • 批准号:
    10619176
  • 财政年份:
    2023
  • 资助金额:
    $ 25.59万
  • 项目类别:
Estrogen Signaling in the Ventromedial Hypothalamus Modulates Adipose Tissue Metabolic Adaptation
下丘脑腹内侧区的雌激素信号调节脂肪组织代谢适应
  • 批准号:
    10604611
  • 财政年份:
    2023
  • 资助金额:
    $ 25.59万
  • 项目类别:
Obesity and Childhood Asthma: The Role of Adipose Tissue
肥胖和儿童哮喘:脂肪组织的作用
  • 批准号:
    10813753
  • 财政年份:
    2023
  • 资助金额:
    $ 25.59万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了