GENOMIC AND GENETIC APPROACHES TO PLAQUE RUPTURE

斑块破裂的基因组学和遗传学方法

• 批准号: 7105585
• 负责人: Stephen MARK Schwartz
• 金额: $ 210.43万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7105585
• 关键词: atherosclerosis; atherosclerotic plaque; clinical research; gene expression; genetic polymorphism; genome

DESCRIPTION (provided by applicant): Despite all the advances in atherosclerosis over the last several decades, surprisingly we lack direct evidence of the critical factors controlling the final events that convert an atherosclerotic lesion from a collection of fatty foam cells to an occlusive, ruptured, procoagulant, and life threatening lesion. The bulk of the evidence supports the hypothesis that these final events occur as a result of inflammatory changes in the lesion. This program projects attempts to test that hypothesis by combining newly developed approaches that allow us to directly visualize the plaque non-invasively in humans with experimental models in the mouse. The human studies will utilize state of the art genomics, including single nucleotide polymorphisms and expression arrays to determine the correlation of specific inflammatory genes with plaque progression. The animal studies will utilize a mouse model of plaque rupture to examine the role of the same genes as manifest in the plaque macrophage and the endothelial cell in these final critical events.

描述（由申请人提供）： 尽管动脉粥样硬化在过去几十年里取得了所有进展，但令人惊讶的是，我们缺乏控制最终事件的关键因素的直接证据，这些最终事件将动脉粥样硬化病变从脂肪泡沫细胞的集合转变为闭塞、破裂、促凝血和危及生命的病变。 大量证据支持这样的假设：这些最终事件是由于病变部位炎症变化而发生的。 该项目试图通过将新开发的方法与小鼠实验模型相结合来检验这一假设，这些方法使我们能够以非侵入性方式直接观察人类斑块。 人类研究将利用最先进的基因组学，包括单核苷酸多态性和表达阵列来确定特定炎症基因与斑块进展的相关性。 动物研究将利用斑块破裂的小鼠模型来检查斑块巨噬细胞和内皮细胞中表现出的相同基因在这些最终关键事件中的作用。

项目成果

Combined analysis of monocyte and lymphocyte messenger RNA expression with serum protein profiles in patients with scleroderma.

硬皮病患者单核细胞和淋巴细胞信使 RNA 表达与血清蛋白谱的联合分析。

• 发表时间: 2008-05
• 作者: Duan, Hangjun;Fleming, Jo;Pritchard, David K;Amon, Lynn M;Xue, Jun;Arnett, Heather A;Chen, Guang;Breen, Patricia;Buckner, Jane H;Molitor, Jerry A;Elkon, Keith B;Schwartz, Stephen M
• 通讯作者: Schwartz, Stephen M

Progression and disruption of advanced atherosclerotic plaques in murine models.

小鼠模型中晚期动脉粥样硬化斑块的进展和破坏。

• 发表时间: 2008-03
• 影响因子: 3.2
• 作者: Rosenfeld, Michael E;Averill, Michelle M;Bennett, Brian J;Schwartz, Stephen M
• 通讯作者: Schwartz, Stephen M

Reader and platform reproducibility for quantitative assessment of carotid atherosclerotic plaque using 1.5T Siemens, Philips, and General Electric scanners.

使用 1.5T 西门子、飞利浦和通用电气扫描仪定量评估颈动脉粥样硬化斑块的读取器和平台再现性。

• 发表时间: 2007-08
• 作者: Saam, Tobias;Hatsukami, Thomas S;Yarnykh, Vasily L;Hayes, Cecil E;Underhill, Hunter;Chu, Baocheng;Takaya, Norihide;Cai, Jianming;Kerwin, William S;Xu, Dongxiang;Polissar, Nayak L;Neradilek, B;Hamar, Wendy K;Maki, Jeffrey;Shaw, Dennis W;Buck
• 通讯作者: Buck

Arterial remodeling in [corrected] subclinical carotid artery disease.

[纠正]亚临床颈动脉疾病中的动脉重塑。

• 发表时间: 2009-12
• 作者: Underhill, Hunter R;Yuan, Chun;Yarnykh, Vasily L;Chu, Baocheng;Oikawa, Minako;Polissar, Nayak L;Schwartz, Stephen M;Jarvik, Gail P;Hatsukami, Thomas S
• 通讯作者: Hatsukami, Thomas S

Association between Snoring and High-Risk Carotid Plaque Features.

打鼾与高风险颈动脉斑块特征之间的关联。

• 发表时间: 2017-08
• 作者: Kirkham, Erin M;Hatsukami, Thomas S;Heckbert, Susan R;Sun, Jie;Canton, Gador;Yuan, Chun;Weaver, Edward M
• 通讯作者: Weaver, Edward M