| Vascular dysfunction is due to a conglomerate of mechanisms. We have chosen to study long-term vascular dysfunction (years), such as resulting from diabetes mellitus, middle term dysfunction as pre-eclampsia, and short-term vascular dysfunction (hours, days) such as resulting from sepsis. The research consists of 4 main topics: 1) the pathogenesis and treatment of cardiovascular and renal complications of diabetes mellitus, hypertension and dyslipidaemia; 2) the pathogenesis and treatment of cardiovascular and renal complications of hyperhomocysteinaemia; 3) gender differences in the susceptibility to cardiovascular disease and cardiovascular effects of sex steroids; and 4) the pathogenesis and treatment of circulatory maladaptation in pregnancy. Patients with diabetes mellitus often have hypertension and dyslipidaemia. It is likely that the interactions among these risk factors are responsible for the excess of cardiovascular and renal disease among diabetic patients. The effects of these interactions on vascular disease are studied at various levels, i.e. epidemiologically (with the EMGO Institute and with other partners), clinically (using non-invasive methods such as ultrasound, impedance plethysmography and videomicroscopy), in animal models and in vitro (using cell culture systems). Hyperhomocysteinaemia is a recently described atherogenic and thrombogenic risk factor that may be present in 5-10% of the general population. The pathogenesis of hyperhomocysteinaemia-associated vascular disease is poorly understood but may involve the vascular endothelium at an early stage. Hyperhomocysteinaemia is universally present in (even minimal) renal failure. Research at present focuses upon 1) the epidemiology of hyperhomocysteinaemia (in collaboration with the EMGO-institute and other partners); 2) the effects of hyperhomocysteinaemia on the endothelium and the vascular wall; and 3) its role in the - often rapidly progressive - atherosclerosis observed in patients with renal failure. Atherosclerotic cardiovascular disease is uncommon in premenopausal women as compared to age-matched men, a difference that rapidly disappears after the menopause, thus suggesting a vasoprotective role of oestrogens. In addition, sex steroids may modulate the vascular risk associated with diabetes mellitus. The aim of our research is to investigate: 1) the cardiovascular effects of sex steroids, and 2) the interactions between diabetes and sex steroids. The research program concerning circulatory adaptation in pregnancy focuses on the pathogenesis and treatment of pre-eclampsia, a prime cause of fetal and maternal morbidity and mortality. In general, there is a close collaboration with the Institute for Endocrinology, Reproduction and Metabolism (EVM) and the EMGO-institute, both within the Vrije Universiteit, and externally with the Gaubius Laboratory in Leiden, which is part of TNO-Prevention and Health. |
