It is known that during aging hemodynamic forces associated with the blood circulation, such as pressure and shear stress changes substantially, especially when hypertension develops. The changes greatly affect the function of endothelium and smooth muscle, and the structure of vessels (cellular composition, ECM). Such vascular remodeling can lead to organ dysfunction and further progression of vascular diseases. The primary objective of this project is to elucidate the aging- and hypertension-induced functional and morphological changes in small arterial vessels of the brain.
The following hypotheses will be tested:
1) As a function of age the contractile capacity of vessels increases due to changes in endothelium and smooth muscle vasomotor signaling,
2) The primary changes will involve reduction of endothelium derived nitric oxide synthesis and upregulation of the smooth muscle the arachidonic acid-cythochrome p450 HETE pathway,
3) The vascular smooth muscle content increases together with ECM components, such as collagen, which leads to decreased vascular distensibility.
Training: The ESR will be trained to understand the field of vascular biology, the complexity of the regulation of cerebral circulation and particularly the role of hemodynamic factors in acute adaptation and chronic remodelling. We will apply confocal imaging of ECM/cytoskeleton interaction using novel technology under development by DMT. Also we will use VIS rodent ultrasound technology to measure flow with high resolution, including contrast-enhanced US-Doppler in small vessels, in vivo experiments. Involved partners are LMU, AU, and DMT where the ESR will spend 1 month each to learn their research aims methods and theory and to develop collaborative investigations (cellular signaling, ECM analysis and calcium imaging).
Toth, P., Szarka, N., Farkas, E., Ezer, E., Czeiter, E., Amrein, K., Ungvari, Z., Hartings, J.A., Buki, A., & Koller, A. (2016). Traumatic brain injury-induced autoregulatory dysfunction and spreading depression-related neurovascular uncoupling: Pathomechanisms, perspectives, and therapeutic implications. Am. J. Physiol. Heart Circ. Physiol., 311, 1118-1131.
Ph.D student / post-doc
Prof. Ákos Koller