Age and regional variation of behaviour of blood vessels with different curvature extents

Project aim, objectives and outline
Stiff blood vessels are known to increase risk of heart failure. Earlier studies revealed clear association between the mechanical stiffness of blood vessels and a number of factors including age, smoking, diabetes and obesity. The research has so far concentrated on straight vessel segments and little attention has been given to curved vessels.

The study will start with the elucidations of the effects of different flow patterns and the associated shear stresses on the signalling, gene expression and cellular functions in vascular endothelium, which is the monolayer of cells that lines the luminal surface of blood vessels. A disturbed flow chamber that can produce laminar, pulsatile, and oscillatory flows will be established to provide different flow patterns and associated shear stresses. Vascular endothelial cells (ECs) will be subjected to the created flow conditions, and their signalling and functional modulations will be analysed by a variety of state-of-the-art biochemical techniques. In addition, the mechanical stiffness of curved blood vessels (e.g., aortic arch) associated with different ages of rat, bovine (cow), or porcine (pig) will be measured. A collagen matrix gel system will be constructed to mimic the changes of mechanical stiffness of blood vessels in aging, and vascular ECs will be cultured on the surfaces of these matrix gels with different stiffness to study the regulatory effects of mechanical stiffness on EC behaviour and function.

Experimental testing of rat, bovine or porcine specimens of curved blood vessels will be conducted under near physiologic conditions. The specimens will be obtained fresh from abattoirs, clamped away from curved regions, kept under physiologic conditions of hydration and temperature and subjected to a flow of a saline solution similar to that experienced with blood. The vessel’s displacement behaviour will be monitored using a system of digital cameras, whose images will be correlated to determine the displacement distribution at different flow conditions. Inverse modelling, using finite element analysis, will then be conducted to use the displacement distribution determined experimentally to derive the stress-strain behaviour in different parts of the vessel wall tissue. The modelling will consider the interaction between the blood flow and the mechanical behaviour of the blood vessel, in order to make the analysis representative of in vivo behaviour. The tests and the analysis will be conducted while using vessel specimens with different ages and different curvature values to obtain material characteristics that correlate with the experimental biology analysis.

Expected pattern of study
Following a first year of taught modules either at Liverpool or NTHU, students will be expected to spend approximately 2 years in each institution.

Facilities to be used at NTHU and UoL
The project will benefit from the experimental biology facilities and long experience in blood vessel behaviour at the NTHU and the biomechanical testing facilities and fluid-structure interaction expertise at Liverpool.