1. Physiological and pathophysiological regulation of the human coronary microcirculation
2. Microcirculation in metabolic syndrome, obesity and diabetes mellitus
3. Oxidative stress in the microcirculation
4. Flow/shear stress-dependent regulation of arteriolar diameter in disease
5. Role of arachidonic acid cascade and nuclear receptors in regulation of microcirculation
Flow/shear stress-dependent regulation of coronary arteriolar diameter in patients with diabetes mellitus: We investigate underlying mechanisms responsible for small coronary artery disease in patients with diabetes. We study flow/wall shear stress-induced vasomotor responses of the isolated, coronary arteriole obtained from the heart of diabetic patients undergoing cardiac surgery. Using two-photon confocal microscopy and live cell imaging approaches changes in endothelial nitric oxide and calcium levels are being evaluated in the intact human coronary arteriole.
Angiotensin II receptor trafficking in the microcirculation in health and disease: We aim to understand mechanisms by which angiotensin II receptor trafficking determines the function of resistance arteries under physiological condition as well as in diabetes mellitus. Angiotensin II receptor internalization and recycling is detected in intact small arteries and cultured cells by live cell imaging and fluorescence techniques.
Microparticle-endothelium interaction in inflammation: We aim to develop novel drug delivery approaches to selectively target and interfere with cellular signaling mechanisms in the inflamed coronary endothelium. We apply microparticle-based approaches in intact, pressurized coronary microvessels.
Techniques in use:
1. In vitro videomicroscopy to study isolated, pressurized human microvessels
2. Intravital microscopy of the cremaster muscle and mesentery in animal models
3. Imaging of intracellular calcium in pressurized artery
4. Cell culture of smooth muscle and endothelial cells
5. Immunohystochemistry and Western Blotting applied to microvessels
6. Red blood cell velocity measurements
7. Animal models of metabolic syndrome and diabetes mellitus