Research projects

Over the next two decades, arteriosclerosis and associated cardiovascular disease (CVD) are expected to become the main cause of death and morbidity world-wide. Atheromatous plaque growth is a chronic inflammatory process characterised by excessive cell proliferation. Using genetically modified mice, our group has demonstrated that deactivating the p27 cell growth suppressor increases the proliferation rate in the artery wall and accelerates arteriosclerosis induced by the consumption of a diet rich in fat and cholesterol. Inversely, superexpression of p27 using recombinant adenovirus inhibits the development of obstructive vascular damage in angioplasty in animal models. This and other evidence suggests that p27 is a protein that has atheroprotective properties. From the point of view of the possible diagnostic application of these findings, pilot studies carried out by our group have identified human gene single nucleotide polymorphisms (SNPs): CDKN1B (p27 protein) that are associated with an increased risk of acute myocardial infarction, which very often originates with a coronary arteriosclerosis process. Based on these precedents, the main aim of this proposal is to carry out an in-depth study of the cellular and molecular mechanisms by which p27 exercises its atheroprotective action. This information could give significant insight into identifying new therapeutic targets for the treatment of arteriosclerosis. Furthermore, we also seek to identify genetic variations in the human gene CDKN1B that enable early recognition of individuals with a high risk of suffering an acute coronary accident. If this goal is achieved, a kit would be constructed to examine the diagnostic polymorphic variations identified in our studies in patients.