Lu Hong, Cassis Lisa A, Daugherty Alan
Cardiovascular Research Center, Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40536-0200, USA.
Curr Drug Targets. 2007 Nov;8(11):1181-9. doi: 10.2174/138945007782403829.
Increased blood pressure is a consistent risk factor for the development of atherosclerotic diseases in humans, although the basis for this relationship is unknown. Genetically engineered mice are now commonly used to study mechanisms of atherosclerosis. More recently, blood pressure can be reliably measured in conscious mice using either tail cuff or telemetric techniques. Thus, mouse models permit the investigation of the complex interactions of blood pressure and atherogenesis. Most mouse models exhibiting hypertension have increased atherosclerotic lesion size, although there have been exceptions to these findings. Also, there are several reports that have used methods to decrease blood pressure and demonstrated reduced atherosclerosis. In contrast, there are many studies in which atherosclerosis has been altered without changes in blood pressure, and conversely, studies in which blood pressure changes did not alter atherosclerosis. Studies that have specifically defined the role of elevated systolic blood pressure on the development of atherosclerosis have uniformly demonstrated that pressure per se is not responsible for changes in lesion development. Thus, while increased systolic blood pressure is frequently associated with atherosclerosis, the stimulus for the hypertension appears to be the major determinant of atherogenesis rather than pressure per se. A consistent theme in the literature has been that perturbations of the renin angiotensin system display the strongest correlations between blood pressure and atherosclerosis.
血压升高是人类动脉粥样硬化疾病发生的一个持续危险因素,尽管这种关系的基础尚不清楚。基因工程小鼠现在常用于研究动脉粥样硬化的机制。最近,可以使用尾套或遥测技术在清醒小鼠中可靠地测量血压。因此,小鼠模型允许研究血压与动脉粥样硬化形成的复杂相互作用。大多数表现出高血压的小鼠模型的动脉粥样硬化病变大小增加,尽管这些发现也有例外。此外,有几份报告使用方法降低血压并证明动脉粥样硬化减轻。相反,有许多研究中动脉粥样硬化发生了改变而血压没有变化,反之,血压变化并没有改变动脉粥样硬化的研究也有。专门定义收缩压升高在动脉粥样硬化发展中作用的研究一致表明,压力本身并不是病变发展变化的原因。因此,虽然收缩压升高经常与动脉粥样硬化相关,但高血压的刺激因素似乎是动脉粥样硬化形成的主要决定因素,而不是压力本身。文献中一个一致的主题是肾素血管紧张素系统的扰动在血压和动脉粥样硬化之间表现出最强的相关性。