A stochastic model of cell aggregation under planar flow in the dilute regime

Models of the adhesion of a population of cells in a plane flow are developed, considering the dilute regime. Cells considered as rigid punctual entities are virtually injected at regular times within a plane channel limited by two fixed planes. The pressure profile is supposed to be triangular (constant gradient), in accordance with the assumptions of a Poiseuille flow. The cell adherence to the channel wall is governed by the balance of forces, accounting for gravity, non-specific physical interactions, such as electrostatic effects (repulsive) and Van der Waals forces (attractive), specific adhesive forces representing the ligand–receptor interactions, and friction between cells and the fluid in the vicinity of the endothelium wall. The spatial distribution of the adhesion molecules along the wall is supposed to be a random event, accounted for by a stochastic spatial variability of the dipolar moments of those molecules, according to a Gaussian process. Experimental trends reported for the rate of aggregation of L-selectin mediated leukocytes under shear flow are in qualitative accordance with the evolution versus time of adhering cells obtained by the present simulations. The effect of the maximal injection pressure on those kinetics is assessed.     

Lipogenesis in arterial wall and vascular smooth muscular cells: regulation and abnormalities in insulin-resistance

Background

Vascular smooth muscular cells (VSMC) express lipogenic genes. Therefore in situ lipogenesis could provide fatty acids for triglycerides synthesis and cholesterol esterification and contribute to lipid accumulation in arterial wall with aging and during atheroma.

Methods

We investigated expression of lipogenic genes in human and rat arterial walls, its regulation in cultured VSMC and determined if it is modified during insulin-resistance and diabetes, situations with increased risk for atheroma.

Results

Zucker obese (ZO) and diabetic (ZDF) rats accumulated more triglycerides in their aortas than their respective control rats, and this triglycerides content increased with age in ZDF and control rats. However the expression in aortas of lipogenic genes, or of genes involved in fatty acids uptake, was not higher in ZDF and ZO rats and did not increase with age. Expression of lipogenesis-related genes was not increased in human arterial wall (carotid endarterectomy) of diabetic compared to non-diabetic patients. In vitro, glucose and adipogenic medium (ADM) stimulated moderately the expression and activity of lipogenesis in VSMC from control rats. LXR agonists, but not PXR agonist, stimulated also lipogenesis in VSMC but not in arterial wall in vivo. Lipogenic genes expression was lower in VSMC from ZO rats and not stimulated by glucose or ADM.

Conclusion

Lipogenic genes are expressed in arterial wall and VSMC; this expression is stimulated (VSMC) by glucose, ADM and LXR agonists. During insulin-resistance and diabetes, this expression is not increased and resists to the actions of glucose and ADM. It is unlikely that this metabolic pathway contribute to lipid accumulation of arterial wall during insulin-resistance and diabetes and thus to the increased risk of atheroma observed in these situations.