Furthering our understanding of the redox regulation of Protein Kinase A in the cardiovascular system

心血管疾病是英国的主要死亡原因，在其他西方社会也是如此。随着人口寿命的延长，这种负担会继续增加，当心脏和血管中的氧化剂分子水平增加时，会产生一种重要的蛋白质(称为PKA)，这种蛋白质会发生变化(氧化)。因此，当心血管系统组织中的氧化剂水平发生变化时，PKA可能会在某些时候发生变化，例如在疾病期间。我们认为PKA的这种修饰在导致心血管功能障碍的复杂事件中可能是重要的，包括高血压或心力衰竭。简单地说，这种改变涉及PKA被氧化，我们认为这种改变改变了它的功能，这可能会影响心血管疾病的发展。我们提出的实验将使我们能够更好地了解氧化改变如何改变PKA的活性或功能，以及此后这些变化如何影响心血管疾病的发展。从长远来看，我们预计拟议的研究可能会导致针对PKA的新药来限制心血管疾病的发展。这一点很重要，因为目前缺乏能够充分应对这一常见健康问题的药物疗法。

Cardiovascular disease is the leading cause of death in the UK, as it is in other Western societies. This burden continues to grow as the population lives longer, exerting an important proteins (known as PKA) becomes altered (oxidised) when the levels of oxidant molecules increase in the heart and in blood vessels. Thus, PKA may become altered during times, for example during disease, when oxidant levels in the tissues of the cardiovascular system are changed. We think this modification of PKA may be important in the complex events leading to cardiovascular dysfunction, including high blood pressure (hypertension) or heart failure. In simple terms the alteration involves PKA becoming oxidised and we think this alteration changes how it functions, which likely impacts on the development of cardiovascular disease. We propose experiments that will allow us to better understand how the oxidative alteration modifies the activity or function of PKA, and thereafter how these changes influence the development of cardiovascular disease. In the longer term, we envisage the proposed studies may lead to new drugs that target PKA to limit the development of cardiovascular disease. This is important as currently there is a lack of pharmacotherapy that adequately combats this common health problem.