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相关概念视频

Coronary Artery Disease I: Introduction01:30

Coronary Artery Disease I: Introduction

55
Coronary Artery Disease (CAD): An Overview with Scientific InsightsCoronary Artery Disease (CAD), often referred to as C-A-D, is a prevalent blood vessel disorder classified under the broader category of atherosclerosis. Atherosclerosis is a pathological process characterized by the hardening and narrowing of arteries due to the accumulation of atherosclerotic plaques. These plaques are composed of cholesterol, fatty substances, inflammatory cells, calcium, and fibrin, reducing blood flow to...
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Coronary Artery Disease II: Pathophysiology01:26

Coronary Artery Disease II: Pathophysiology

34
Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
34
Atherosclerosis I: Introduction01:30

Atherosclerosis I: Introduction

77
Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
77
Peripheral Artery Disease I: Introduction01:30

Peripheral Artery Disease I: Introduction

32
Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs, particularly the arteries supplying the thighs and calves. In rare cases, it may involve other arteries, including those in the arms.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty...
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lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

8.9K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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Coronary Artery Disease III: Clinical Manifestations01:30

Coronary Artery Disease III: Clinical Manifestations

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Coronary Artery Disease (CAD) is a primary health risk worldwide, leading to significant morbidity and mortality. The condition arises from the buildup of atherosclerotic plaques within the coronary arteries, resulting in diminished blood supply to the heart muscle.The clinical manifestations of CAD vary widely, from asymptomatic stages to severe, life-threatening conditions. Understanding these manifestations is crucial for early diagnosis and effective management.Angina Pectoris: The Warning...
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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
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LIPA,冠状动脉疾病的风险局部:解码变体与功能关系.

Fang Li1, Elise Flynn2,3, Philip Ha1

  • 1Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, 630 West 168th St, P&S 10-401, New York, NY 10032, USA.

European heart journal
|August 19, 2025
PubMed
概括

冠状动脉疾病风险等位基因增加了巨细胞中的脂酶A (LIPA) 表达,使动脉样硬化恶化. 这项研究将LIPA变异与单细胞/巨细胞功能和疾病进展联系起来,提供了机理性的见解.

关键词:
动脉样硬化是一种动脉样硬化.功能性基因组学是一种功能性基因组学.在GWAS中,GWAS就是GWAS.Lysosomal 酸脂酶是一种溶解酶.巨细胞是一个巨细胞.

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科学领域:

  • 基因组学就是基因组学.
  • 分子生物学分子生物学
  • 心血管疾病研究研究

背景情况:

  • 全基因组关联研究确定LIPA是冠状动脉疾病 (CAD) 风险位.
  • 以前的研究优先考虑LIPA作为可能的因果基因,但缺乏功能性证据.
  • 了解LIPA位点的变异与功能关系对于对CAD的机制性见解至关重要.

研究的目的:

  • 在LIPA locus.建立变异与功能关系.
  • 阐明相关的因果变异,调节机制和细胞类型.
  • 为了确定LIPA对动脉样硬化的因果影响.

主要方法:

  • 利用了全基因组后关联研究管道和分子生物学技术 (例如eQTL,Tri-HiC,CRISPRi).
  • 研究了增强剂-促进剂相互作用和转录因子结合 (PU.1).
  • 产生的骨髓细胞特异性Lipa过度表达小鼠 (Ldlr-/-) 以模拟动脉样硬化.

主要成果:

  • 冠状动脉疾病风险等位基因通过增强的PU.1与内部增强剂结合,增加单细胞/巨细胞中的LIPA表达和酶活性.
  • 在小鼠中,骨髓细胞特异性Lipa过度表达导致了更大的动脉样硬化病变.
  • 观察到变化的巨细胞功能,损伤性巨细胞积累的增加,以及特定基因通路的变化.

结论:

  • 在LIPA风险等位基因和单细胞/巨细胞LIPA增加之间建立了直接的因果关系.
  • 证明 LIPA 的增加会加剧动脉样硬化.
  • 将人类功能基因组证据与CAD的机械学理解联系起来.