在人类心脏中的 ангиотензин转化酶. 删除/插入多态的效应
A H Danser1, M A Schalekamp, W A Bax
1Cardiovasculair Onderzoeksinstituut Erasmus Universiteit Rotterdam, COEUR, Erasmus University, Netherlands.
Circulation
|September 15, 1995
概括
血管激素转化酶 (ACE) 删除多态性与DD基因型个体中较高的心脏ACE活性有关. 这可能解释了与这种ACE基因变异相关的心血管疾病风险增加.
科学领域:
- 心血管遗传学 心血管遗传学
- 分子心脏病学分子心脏病学
背景情况:
- 血管激素转化酶 (ACE) 基因插入/删除 (I/D) 多态影响血ACE水平.
- 这种多态性涉及到心血管疾病,如心肌梗塞和冠状动脉疾病.
研究的目的:
- 为了研究ACE基因多态和心脏ACE活性之间的关系.
- 探索将ACE基因型与心血管疾病风险联系起来的潜在机制.
主要方法:
- 在71名非心脏病死亡患者中确定心脏ACE活性和ACE基因型.
- 分析了不同ACE基因型 (DD,ID,II) 的ACE活性.
主要成果:
- 与ID (8.7 mU/g) 和II (9.1 mU/g) 基因型相比,DD基因型 (12.7 mU/g) 的受试者心脏ACE活性显著更高 (P < .01).
- 这种关联独立于性别,年龄和组织采集时间.
结论:
- DD基因型与最高的心脏ACE活性有关.
- 心脏ACE活性升高可能会增加心脏血管新生素II水平,这可能是ACE删除多态和心血管疾病风险之间的关联的基础.
相关概念视频
01:39Mutations
Overview
02:23RNA Editing
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
01:29Heart Failure II: Pathophysiology
Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...