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

心血管疾病是英国死亡的主要原因，在其他西方社会也是如此。随着人口寿命的延长，这种负担继续增长，当心脏和血管中氧化剂分子的水平增加时，重要的蛋白质（称为PKA）就会发生改变（氧化）。因此，PKA可能在心血管系统组织中的氧化剂水平改变时，例如在疾病期间发生改变。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修改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，我们设想拟议的研究可能会导致靶向PKA的新药，以限制心血管疾病的发展。这一点很重要，因为目前缺乏充分对抗这种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.