Nuclear FAK in endothelium: An intrinsic inhibitor of NF-κB activation in atherosclerosis.

Background And Aims: Hyperlipidemia leads to the accumulation of oxidized low-density lipoprotein (oxLDL) within the vessel wall where it causes chronic inflammation in endothelial cells (ECs) and drives atherosclerotic lesions. Although focal adhesion kinase (FAK) is critical in proinflammatory NF-κB activation in ECs, it is unknown if hyperlipidemia alters FAK-mediated NF-κB activity in vivo to affect atherosclerosis progression.

Methods: We investigated changes in EC FAK and NF-κB activation using Apoe mice fed a western diet (WD).

FAK Activation Promotes SMC Dedifferentiation via Increased DNA Methylation in Contractile Genes.

Rationale: Vascular smooth muscle cells (SMCs) exhibit remarkable plasticity and can undergo dedifferentiation upon pathological stimuli associated with disease and interventions.

Objective: Although epigenetic changes are critical in SMC phenotype switching, a fundamental regulator that governs the epigenetic machineries regulating the fate of SMC phenotype has not been elucidated.

Methods And Results: Using SMCs, mouse models, and human atherosclerosis specimens, we found that FAK (focal adhesion kinase) activation elicits SMC dedifferentiation by stabilizing DNMT3A (DNA methyltransferase 3A).

Focal Adhesion Kinase Activity and Localization is Critical for TNF-α-Induced Nuclear Factor-κB Activation.

While sustained nuclear factor-κB (NF-κB) activation is critical for proinflammatory molecule expression, regulators of NF-κB activity during chronic inflammation are not known. We investigated the role of focal adhesion kinase (FAK) on sustained NF-κB activation in tumor necrosis factor-α (TNF-α)-stimulated endothelial cells (ECs) both in vitro and in vivo. We found that FAK inhibition abolished TNF-α-mediated sustained NF-κB activity in ECs by disrupting formation of TNF-α receptor complex-I (TNFRC-I).

Biphasic Postnatal Umbilical Cord Shortening.

Introduction: Variations in postnatal length of refrigerated, unfixed umbilical cords were studied over time to elucidate natural changes and times of stability.

Methods: Length was measured in 132 cords following severance, repeated at varying timed intervals and studied by analysis of variance and regression analysis.

Results: Data show immediate rapid initial phase shortening (mean 4.