In vitro models of atherogenesis
High levels of low density lipoproteins are an important risk factor for the development of atherosclerosis. Atherosclerosis is characterized by a local inflammatory response leading to proliferation of vascular smooth muscle cells and subsequent occlusion of the arterial lumen. We are investigating mechanisms which control growth and activation of human vascular smooth muscle cells. Recent studies in our laboratory have addressed the role of endogenous oxidative stress underlying the growth-promoting effects of native, non-oxidized low density protein.
Sex hormones and atherosclerosis
Estrogens have been implicated in primary prevention of atherosclerosis in premenopausal women and lack of estrogen is associated with an increased risk to develop coronary artery disease in men. Observational studies have suggested that estrogen replacement therapy may reduce the risk for coronary artery disease. These data have been recently challenged by large-scale clinical studies (ERA, HERS, HERS II, WHI) using equine estrogens and methoxyprogesterone acetate (MPA) therapy in elderly postmenopausal women with increased risk for cardiovascular disease. These studies turned out to be negative and showed an increased risk for subsequent cardiovascular events and thrombosis. It is currently unknown whether treatment of postmenopausal women with synthetic drugs can provide cardiovascular protection.
Obesity and cardiovascular disease
In recent years, obesity has become a major health concern in both Western and Eastern countries and is associated with an increased risk for atherosclerosis in general and in young people in particular. Our research in this area has focused on renal and vascular mechanisms which are associated with obesity and we have identified several pathways involved in the disease process. Recent work has shown that obesity independently from blood pressure increases vasoconstriction in an experimental model and that obesity also regulates renal angiotensin converting enzyme. Further research is in progress to determine therapeutic approaches to interfere with cardiovascular alterations which further promote atherosclerosis development in obesity.
All projects are part of our Swiss National Science Foundation-funded research
Cell Biology