Impact of geometric and hemodynamic changes on a mechanobiological model of atherosclerosis.

BACKGROUND AND OBJECTIVE: In this work, the analysis of the importance of hemodynamic updates on a mechanobiological model of atheroma plaque formation is proposed. METHODS: For that, we use an idealized and axisymmetric model of carotid artery. In addition, the behavior of endothelial cells depending on hemodynamical changes is analyzed too. A total of three computational simulations are carried out and their results are compared: an uncoupled model and two models that consider the opposite behavior of endothelial cells caused by hemodynamic changes. The model considers transient blood flow using the Navier-Stokes equation. Plasma flow across the endothelium is determined with Darcy's law and the Kedem-Katchalsky equations, considering the three-pore model, which is also employed for the flow of substances across the endothelium. The behavior of the considered substances in the arterial wall is modeled with convection-diffusion-reaction equations, and the arterial wall is modeled as a hyperelastic Yeoh's material. RESULTS: Significant variations are noted in both the morphology and stenosis ratio of the plaques when comparing the uncoupled model to the two models incorporating updates for geometry and hemodynamic stimuli. Besides, the phenomenon of double-stenosis is naturally reproduced in the models that consider both geometric and hemodynamical changes due to plaque growth, whereas it cannot be predicted in the uncoupled model. CONCLUSIONS: The findings indicate that integrating the plaque growth model with geometric and hemodynamic settings is essential in determining the ultimate shape and dimensions of the carotid plaque.

Impact of hypertension and arterial wall expansion on transport properties and atherosclerosis progression.

This study explored the impact of hypertension on atheroma plaque formation through a mechanobiological model. The model incorporates blood flow via the Navier-Stokes equation. Plasma flow through the endothelium is determined by Darcy's law and the Kedem-Katchalsky equations, which consider the three-pore model utilized for substance flow across the endothelium. The behaviour of these substances within the arterial wall is described by convection-diffusion-reaction equations, while the arterial wall itself is modelled as a hyperelastic material using Yeoh's model. To accurately evaluate hypertension's influence, adjustments were made to incorporate wall compression-induced wall compaction by radial compression. This compaction impacts three key variables of the transport phenomena: diffusion, porosity, and permeability. Based on the obtained findings, we can conclude that hypertension significantly augments plaque growth, leading to an over 400% increase in plaque thickness. This effect persists regardless of whether wall mechanics are considered. Tortuosity, arterial wall permeability, and porosity have minimal impact on atheroma plaque growth under normal arterial pressure. However, the atheroma plaque growth changes dramatically in hypertensive cases. In such scenarios, the collective influence of all factors-tortuosity, permeability, and porosity-results in nearly a 20% increase in plaque growth. This emphasizes the importance of considering wall compression due to hypertension in patient studies, where elevated blood pressure and high cholesterol levels commonly coexist.

Chlorin e6-Conjugated Mesoporous Titania Nanorods as Potential Nanoplatform for Photo-Chemotherapy.

Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O2. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects. In this work, mesoporous titania nanorods were surface-immobilized with Chlorin e6 (Ce6) conjugated through 3-(aminopropyl)-trimethoxysilane as a coupling agent. The mesoporous nanorods act as nano vehicles for doxorubicin delivery, and the Ce6 provides a visible light-responsive production of ROS to induce PDT. The nanomaterials were characterized by XRD, DRS, FTIR, TGA, N2 adsorption-desorption isotherms at 77 K, and TEM. The obtained materials were tested for their singlet oxygen and hydroxyl radical generation capacity using fluorescence assays. In vitro cell viability experiments with HeLa cells showed that the prepared materials are not cytotoxic in the dark, and that they exhibit photodynamic activity when irradiated with LED light (150 W m-2). Drug-loading experiments with doxorubicin (DOX) as a model chemotherapeutic drug showed that the nanostructures efficiently encapsulated DOX. The DOX-nanomaterial formulations show chemo-cytotoxic effects on Hela cells. Combined photo-chemotoxicity experiments show enhanced effects on HeLa cell viability, indicating that the conjugated nanorods are promising for use in combined therapy driven by LED light irradiation.

Characterizing atherosclerotic tissues: in silico analysis of mechanical properties using intravascular ultrasound and inverse finite element methods.

Atherosclerosis is a prevalent cause of acute coronary syndromes that consists of lipid deposition inside the artery wall, creating an atherosclerotic plaque. Early detection may prevent the risk of plaque rupture. Nowadays, intravascular ultrasound (IVUS) is the most common medical imaging technology for atherosclerotic plaque detection. It provides an image of the section of the coronary wall and, in combination with new techniques, can estimate the displacement or strain fields. From these magnitudes and by inverse analysis, it is possible to estimate the mechanical properties of the plaque tissues and their stress distribution. In this paper, we presented a methodology based on two approaches to characterize the mechanical properties of atherosclerotic tissues. The first approach estimated the linear behavior under particular pressure. In contrast, the second technique yielded the non-linear hyperelastic material curves for the fibrotic tissues across the complete physiological pressure range. To establish and validate this method, the theoretical framework employed in silico models to simulate atherosclerotic plaques and their IVUS data. We analyzed different materials and real geometries with finite element (FE) models. After the segmentation of the fibrotic, calcification, and lipid tissues, an inverse FE analysis was performed to estimate the mechanical response of the tissues. Both approaches employed an optimization process to obtain the mechanical properties by minimizing the error between the radial strains obtained from the simulated IVUS and those achieved in each iteration. The second methodology was successfully applied to five distinct real geometries and four different fibrotic tissues, getting median R 2 of 0.97 and 0.92, respectively, when comparing the real and estimated behavior curves. In addition, the last technique reduced errors in the estimated plaque strain field by more than 20% during the optimization process, compared to the former approach. The findings enabled the estimation of the stress field over the hyperelastic plaque tissues, providing valuable insights into its risk of rupture.