Abstract

Cardiovascular disease is a leading cause of death throughout the world. The demand for new therapeutic interventions is increasing. Although pharmacological and surgical interventions dramatically improve the quality of life of cardiovascular disease patients, cheaper and less invasive approaches are always preferable. Biomaterials, both natural and synthetic, exhibit great potential in cardiac repair and regeneration, either as a carrier for drug delivery or as an extracellular matrix substitute scaffold. In this review, we discuss the current treatment options for several cardiovascular diseases, as well as types of biomaterials that have been investigated as potential therapeutic interventions for said diseases. We especially highlight investigations into the possible use of conductive polymers for correcting ischemic heart disease-induced conduction abnormalities, and the generation of biological pacemakers to improve the conduction pathway in heart block.

Abstract

Millions of people are exposed to arsenic through their drinking water and food, but the mechanisms by which it impacts embryonic development are not well understood. Arsenic exposure during embryogenesis is associated with neurodevelopmental effects, reduced weight gain, and altered locomotor activity, and in vitro data indicates that arsenic exposure inhibits stem cell differentiation. This study investigated whether arsenic disrupted the Wnt3a signaling pathway, critical in the formation of myotubes and neurons, during the differentiation in P19 mouse embryonic stem cells. Cells were exposed to 0, 0.1, or 0.5 μM arsenite, with or without exogenous Wnt3a, for up to 9 days of differentiation. Arsenic exposure alone inhibits the differentiation of stem cells into neurons and skeletal myotubes, and reduces the expression of both β-catenin and GSK3β mRNA to ∼55% of control levels. Co-culture of the arsenic-exposed cells with exogenous Wnt3a rescues the morphological phenotype, but does not alter transcript, protein, or phosphorylation status of GSK3β or β-catenin. However, arsenic exposure maintains high levels of Hes5 and decreases the expression of MASH1 by 2.2-fold, which are anti- and pro-myogenic and neurogenic genes, respectively, in the Notch signaling pathway. While rescue with exogenous Wnt3a reduced Hes5 levels, MASH1 levels stay repressed. Thus, while Wnt3a can partially rescue the inhibition of differentiation from arsenic, it does so by also modulating Notch target genes rather than only working through the canonical Wnt signaling pathway. These results indicate that arsenic alters the interplay between multiple signaling pathways, leading to reduced stem cell differentiation.