Publications

Atrial fibrillation (AF) is a heterogeneous disease that presents in a wide range of clinical scenarios. Correspondingly, a diverse array of large animal models has developed for the study of AF. Different atrial substrate exists in these models, and quantitative analysis of the AF that develops in each case reveals unique characteristics. This article reviews the defining properties of several prominent AF animal models, with a focus on how spatiotemporal organization can discriminate between AF substrates. It addresses how spatiotemporal assessments have been extended to human AF and discusses the insights gained from these new analyses.

BACKGROUND

The ontogenesis of the epidermal permeability barrier is complex and incompletely understood. Previously we showed that IL-1 and TNFalpha regulate permeability barrier homeostasis in adult mice.

OBJECT

We determined whether IL-1 and TNFalpha also regulate fetal barrier development.

METHODS

Messenger RNA and protein levels in epidermis were determined by real-time PCR and immunohistochemistry, respectively. Epidermal ultra-structure was examined by electron microscopy.

RESULTS

The protein expression of IL-1alpha/beta and TNFalpha peaked in fetal rat epidermis at gestational age d19-20, a time point that coincides with the formation of a competent barrier. Treatment of fetal rat explants with IL-1 or TNFalpha accelerates barrier formation in a time- and dose-related fashion, evidenced by a decrease in transepidermal water loss attributable to the presence of mature morphology and an increase in the expression of cornified envelope proteins. Using single receptor KO mice, we demonstrated a delay in both barrier formation and cornified envelope protein expression, paralleled with immature lamellar membranes in epidermis of IL-1R KO, but not TNFR KO vs. wild-type at day 17, differences that disappeared in later gestational stages and immediately after birth. Using TNF receptor and IL-1 receptor double knock out (D-KO) mice, we further demonstrated that a transient delay in barrier development consistently occurs in epidermis of D-KO mice.

CONCLUSION

IL-1 plays a role in regulating the late stages of SC formation and permeability barrier ontogenesis.