Molecular Internal Medicine

Our research has three major areas:

Disease Modifiers of Atherogenesis
Coronary heart disease and stroke are the most prevalent causes of death worldwide. Part of our research is aimed to identify and characterize new factors involved in the atherosclerosis process and to test their relevance for human disease. For our studies, we utilize transgenic models of disease and also generate our own transgenic models. We have recently identified and charaterized a secretase-like protein which plays a role in atherogenesis and inflammation. Further research in this area is ongoing.

Obesity as a Risk Factor for Chronic Disease
Obesity is one of today´s major health concern and associated with an increased risk for atherosclerosis in general and in young people in particular. Our research in this area is directed towards the identification of pathomechanisms which are associated with organ injury by obesity. So far, we have identified abnormalities related to vasoconstriction and inflammation in the vasculature, kidney, fat tissue, and liver. We are currently studying obesity during childhood and adulthood and exploring whether pathological changes observed are reversible or not. We expect to find clues to the disease processes and their reversibility that may be important to diagnosis and therapy. We are also studying mechanisms of vascular insulin resistance.

Mechanisms Underlying Cardiovascular Sex Differences
Endogenous estrogens are protective from coronary heart disease in women. Our research in this area aims at identifying novel estrogen-dependent pathways and characterizing abnormalities in the vascular wall during atherogenesis. For our studies we utilize transgenic models as well as human tissue for our clinical studies. Recent work has lead to the identification of the first G protein-coupled estrogen receptor (GPER) as a modifier of blood pressure and vascular cell function. Further research in this area is ongoing.

More information is available at the University of Zurich Research database.

Specific areas include

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 methoxyprogesteroneacetate (MPA) replacement therapy in 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.

Vascular physiology of atherosclerosis
Impairment of endothelium dependent vasodilation is a key feature of cardiovascular risk factors and overt atherosclerosis. Several endothelium-derived factors such as nitric oxide, angiotensin II, endothelin-1, and others have been identified to importantly contribute to this disease process. In our laboratory, we are investigating mechanisms underlying this impairment of endothelial cell function. The aim of research in this area is to identify novel pathways involved in functional abnormalities in the vascular wall and predisposing to atherogenesis as target for new therapeutic approaches.

Vasomotor tone control of human blood vessels
In order to complement data obtained in experimental models, we use human blood vessels to determine whether these mechanisms of functional vascular abnormalities also play a role in the human vasculature. Recently, research in this area has been particular focused on the role of estrogen receptors on vascular and vasoactive pepides such as endothelin-1 on the function in human arteries and veins.

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 the endothelin receptors. 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