Cardiovascular Function and Biomechanics in HHcy

Unknown Cauchy stress vs stretch behavior in the longitudinal direction of representative aortas from rabbits fed with standard diet (green), HHcy (black), HCL (blue, and HHcy/HCL diets (red) for 10 weeks.

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Among CVD, ischemic heart disease, stroke and peripheral artery disease, the main factor of which is atherosclerosis, remain the most common manifestations of CVD. Atherosclerosis is a chronic inflammatory disease that occurs primarily in large and medium-sized elastic and muscular arteries and leads to progressive thickening and stiffening of the artery wall. This latter is mainly caused by an alteration in collagen/elastin organization.

Currently, only half of all cases of atherosclerosis can be explained by established risk factors, including hypercholesterolemia (HCL). In addition to the well-known traditional risk factors, hyperhomocysteinemia (HHcy), characterized by an increased concentration of homocysteine (Hcy) in the plasma, has emerged as a new independent risk factor for atherosclerosis. In addition, HHcy has also been linked to an increased risk of myocardial infarction in several studies. Since the role of HHcy in atherosclerosis is not well understood and the treatment of HHcy-associated consequences has not yet been investigated, the main aim of this research project is to clarify how this independent risk factor influences the biomechanical properties of the aorta and myocardium.

To this end, mechanical tests are performed with a wide range of loading rates and applied strains, as well as microstructural studies on aortic and myocardial samples collected from rabbits fed with different types of diets affecting both plasma Hcy content and the onset of arteriosclerosis. In a previous study examining the influence of HHcy on rabbit aortic tissues, it was shown that the HHcy diet was sufficient to induce stiffening of the aorta even in the absence of HCL. In addition, this study demonstrates that the combination of HHcy and HCL produces greater aortic wall thickening and tissue atherogenic transformation compared to the standard diet. To diagnose CVD in HHcy and to realize novel therapy and prevention strategies, the experimental activity will be combined with computations. In the second part of the project, experimental data will be used to develop a mathematical model to understand if and how HHcy affects the biomechanical properties of the aorta and myocardium in rabbits.

The long-term goal is to use the proposed mathematical model to analyse the influence of further plasma Hcy concentrations on the biomechanical properties of aortic and myocardial tissue in silico.

Funding: Austrian Science Fund (FWF)