At Yale University, we studied biaxial arterial biomechanics using the current state-of-the-art methodology. This has led to several novel findings. First, we discovered a key role of the genetic background in arterial remodelling with hypertension. Second, further studying this, we found strong evidence that this role of genetic background is through differences in arterial contractility, modulating the arterial inflammatory response. Third, in a related project, we showed that when ageing and hypertension are combined in murine models, ageing has a more pronounced effect than hypertension on arterial stiffening.
While working on these projects, we implemented from scratch a thick-walled, bi-layered model of arterial wall mechanics, including an explicit model of active smooth muscle contraction. This was extended into a growth and remodelling formulation, where such smooth muscle contraction modulates arterial tone and in turn influences arterial remodelling and inflammation.
In parallel, through collaboration with Maastricht University, we studied the effects of the diabetes-related crosslinking effects of methylglyoxal (MGO), one of the most potent AGE precursors, in multiple studies. First, we performed a literature review and found that in the current literature, there is no direct evidence to date of an association between MGO or MGO-derived advanced glycation end-products, and arterial stiffening. Second, in a preclinical study, we investigated how oral MGO supplementation influenced arterial stiffness. Third, we tested how direct incubation of an artery in a high-concentration MGO solution alters its mechanics. Fourth, in a clinical cross-sectional cohort study, we assessed whether there was an association between plasma MGO concentration and arterial stiffness. Finally, in a clinical study, we assessed whether pyridoxamine, an AGE inhibitor, attenuated arterial stiffening. We did not observe such effect.
At Maastricht University, we also preclinically studied the effects of arterial calcification on arterial stiffness by comparing groups subjected to different durations of warfarin treatment (inducing calcification). We are currently working on modelling these results. We also developed a methodology to reliably quantify the vascular smooth muscle cell density in the arterial wall, based on two-photon laser scanning microscopy.
In parallel, we have implemented a novel quasi-linear viscoelasticity model that is able to capture and integrate our set-up’s quasi-static as well as dynamic data separately in terms of collagen and elastin. Finally, we have thoroughly assessed current methods of modelling smooth muscle contraction and discovered a potential instability in many of the approaches currently in use in the field.
Findings from this project were disseminated at multiple international (European and beyond) conferences, both to an engineering audience (World Congress of Biomechanics; Summer Biomechanics, Bioengineering, and Biotransport Conference) as well as more clinical audiences (e.g. ARTERY, European/International Societies of Hypertension, North American Artery). Further outreach was performed through Pint of Science, a Dutch radio interview, and Twitter, as well as through the project website.
