The histone demethylase PHF8 facilitates alternative splicing of the histocompatibility antigen HLA-G.

Histone3-lysine9 (H3K9) residues not only control gene expression, but also contribute to RNA splicing. Here, the H3K9 histone demethylase PHF8 was investigated in endothelial cells for its involvement in alternative splicing. An angiogenic sprouting assay shows the importance of PHF8 for endothelial cells.

The histone demethylase Jarid1b mediates angiotensin II-induced endothelial dysfunction by controlling the 3'UTR of soluble epoxide hydrolase.

Aim: The histone demethylase Jarid1b limits gene expression by removing the active methyl mark from histone3 lysine4 at gene promoter regions. A vascular function of Jarid1b is unknown, but a vasoprotective function to inflammatory and hypertrophic stimuli, like angiotensin II (AngII) could be inferred. This hypothesis was tested using Jarid1b knockout mice and the inhibitor PBIT.

The Histone Demethylase PHF8 Is Essential for Endothelial Cell Migration.

Epigenetic marks critically control gene expression and thus the cellular activity state. The functions of many epigenetic modifiers in the vascular system have not yet been studied. We screened for histone modifiers in endothelial cells and observed a fairly high expression of the histone plant homeodomain finger protein 8 (PHF8).

Epigenetic Regulation of Angiogenesis by JARID1B-Induced Repression of HOXA5.

Objective: Altering endothelial biology through epigenetic modifiers is an attractive novel concept, which is, however, just in its beginnings. We therefore set out to identify chromatin modifiers important for endothelial gene expression and contributing to angiogenesis.

Approach And Results: To identify chromatin modifying enzymes in endothelial cells, histone demethylases were screened by microarray and polymerase chain reaction.

Intermedin ameliorates atherosclerosis in ApoE null mice by modifying lipid profiles.

Intermedin (IMD) is a recently discovered vasodilator peptide. We studied the role of IMD in the pathogenesis of atherosclerosis by investigating the ability of exogenous IMD to alter lipid profiles and ameliorate the development of atherogenic-diet induced atherosclerosis in ApoE-/- mice. Ten of eight-week-old male C57BL/6J mice were as control.

Disruption of CD38 gene enhances cardiac functions by elevating serum testosterone in the male null mice.

Aims: Gender-related phenotypes in the cardiovascular system have been observed in various genetically modified mice. Here, we report that cardiac functions are significantly improved only in male CD38-null mice and we explore the potential mechanisms of the sexual dimorphism mediated by CD38 deficiency.

Main Methods: Cardiac functions of mice were measured by pressure-volume conductance catheter technique and echocardiography.

Mouse embryonic fibroblasts from CD38 knockout mice are resistant to oxidative stresses through inhibition of reactive oxygen species production and Ca(2+) overload.

CD38 is a multifunctional enzyme that has both ADP-ribosyl cyclase and cADPR hydrolase activities, being capable of cleaving NAD(+) to cyclic ADP ribose (cADPR) and hydrolyzing cADPR to ADPR. It has been reported that there is markedly a reduction of cADPR and elevation of NAD in many tissues from CD38 knockout (CD38(-/-)) mice. Cyclic ADPR is a potent second messenger for intracellular Ca(2+) mobilization, and NAD is a key cellular metabolite for cellular energetic and a crucial regulator for multiple signaling pathways in cells.