血管新生因高胆固醇血症而受损:不对称的二甲基氨基氨酸的作用
1Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305-5406, USA.
Circulation
|September 20, 2000
概括
高胆固醇会通过增加非对称二甲基氨基 (ADMA) 的水平而损害血管生长 (血管生成),这是一种氧化 (NO) 合成酶抑制剂. 用L-氨酸补充剂逆转了这种效果,证实了ADMA的存在.
科学领域:
- 心血管生物学 心血管生物学
- 内皮细胞功能 内皮细胞功能
- 血管生物学 血管生物学
背景情况:
- 由内皮衍生的氧化 (NO) 对许多血管性因素至关重要.
- 非对称二甲基氨基 (ADMA) 是NO合成酶的内源性竞争性对手.
- 高胆固醇血症与ADMA水平升高有关,减少了NO合成.
研究的目的:
- 为了调查高胆固醇血症是否通过ADMA依赖的机制损害血管生成.
- 确定ADMA在脂质诱导的血管生成功能障碍中的作用.
主要方法:
- 在正常和非脂蛋白E缺乏高胆固醇血症小鼠中使用皮下磁盘植入系统评估血管生成.
- 测量纤维血管生长作为血管生成的指标.
- 口服L-氨酸或L-尼托氨酸,并直接将ADMA注入磁盘.
主要成果:
- 血管生成在高胆固醇血清小鼠中受损,与血ADMA升高相关.
- 口服L-氨酸的使用逆转了高胆固醇贫血小鼠的血管功能障碍.
- 阿德玛直接抑制了血管生成,这种效应被L-阿尔吉尼因逆转.
结论:
- 与高胆固醇血相关的NO合成酶通路障碍会损害血管生成.
- ADMA被认为是血管生成的内源性抑制剂.
- 这些发现表明ADMA调解脂质诱导的血管新生障碍,可通过L-阿尔金因来逆转.
更多相关视频
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.9K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
Cholesterol: Significance and Regulation
2.1K
Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Considering cholesterol and...
2.1K
Coronary Artery Disease I: Introduction
1.8K
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...
1.8K
Coronary Artery Disease II: Pathophysiology
1.1K
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...
1.1K
Atherosclerosis I: Introduction
2.5K
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...
2.5K
Atherosclerosis III: Management
741
Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
741


