Vascular Stress
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Partner: Ferdinand le Noble (MDC Berlin-Buch), Gilbert Schönfelder (Charité), Michael Bader (MDC, Berlin-Buch), Norbert Hübner (MDC, Berlin- Buch), Heinz-Peter Schultheiss (Charité)
For a major group of vascular diseases (arteriosclerosis, myocardial infarction, stroke, hypertension, tumours) and clinically relevant adaptations (wound healing, development, aging, exercise) vascular reactions to hemodynamic, inflammatory, oxidative or metabolic stimuli play an important role. In this context all functional and pathologic scenarios are seen as vascular stressors, as long as they increase vascular load. Frontiers between functionally adequate response and maladaptation are fluent and are determined by the type of stimuli, genetic predisposition and other protective or harmful factors.
The vascular wall is a flexible and integrating organ consisting of cellular components (endothelial cells, smooth muscle cells, cells of the adventitia and fibroblasts) and the extracellular matrix. Within the process of vascular remodelling number and form of all components of the vascular wall are continuously varied resulting in a structural reorganisation of the vascular wall. It responds to physiologic stimuli to guarantee its stability under normal conditions. In the case of cardiovascular disease pathological stimuli cause maladaptation of the vascular wall.
Schematic representation of the CCR focus "Vascular Stress". Tissue remodelling of the vascular wall is based on the capability of the artery to alter in size and shape, and occurs in response to numerous stress factors. This CCR focus addresses aspects of pathological inward remodelling in terms of atherosclerosis, restenosis and transplant vasculopathy, as well as outward remodelling regarding arteriogenesis and aneurysm formation. Integrating both clinicians and basic scientists we are focussing at unravelling the biological and molecular basis of these physiological and pathological remodelling processes, which should pave the way for developing therapeutic and preventive strategies for the benefit of patients suffering or not yet suffering from vascular disease. The involved principle investigators at the CCR are listed along the sphere.
Within the Research Focus "Vascular Stress"at the CCR clinicians and basic scientists are working together to understand physiological and pathophysiological remodelling of the vascular wall.
A number of current research projects address topics in the field of "Vascular Stress". Some of the house intern co-operations were initiated within the European early stage research training programm "Cardiovasc". Within the CCR "Vascular Stress" focus an interdisciplinary team of researchers (internists, cardiologists, nephrologists, cell biologists, biochemists, physiologists and pharmacologists) is studying vascular changes in different organs (heart, brain, kidney, aorta and extremities). Diseases like stroke, myocardial infarction, cardiac hypertrophy, aortic aneurisms, cardiac, retinal or nephrotic changes due to adipositas or diabetes, chonic kidney disease, glomerulosclerosis, transplant vasculopathy but also beneficial adaptations like arteriogenesis after stenosis are explored. On a molecular level, contributions of the renin-angiotensin-aldosteron-system. NO-cGMP-, TGF beta-, endothelin- estrogen- and PPAR ( Peroxisom-Proliferator-Activated Receptor)- and HIF (hypoxia-inducible factors)-mediated signal transduction pathways are investigated.
One of the major claims of the research focus "Vascular Stress" is the advancement of internal and external co-operations in order to increase the quality of scientific output. This is why the research focus concentrates on projects which need the expertise of two or more groups.