Cardiac deficiency of P21-activated kinase 1 promotes atrial arrhythmogenesis in mice following adrenergic challenge.

P21-activated kinase 1 (Pak1) signalling plays a vital and overall protective role in the heart. However, the phenotypes of deficiency in the cardiac atria have not been well explored. In this study, cardiac-conditional knock-out (cKO) mice were studied under baseline and adrenergic challenge conditions.

Identification of a Monoclonal Antibody That Attenuates Antiphospholipid Syndrome-Related Pregnancy Complications and Thrombosis.

In the antiphospholipid syndrome (APS), patients produce antiphospholipid antibodies (aPL) that promote thrombosis and adverse pregnancy outcomes. Current therapy with anticoagulation is only partially effective and associated with multiple complications. We previously discovered that aPL recognition of cell surface β2-glycoprotein I (β2-GPI) initiates apolipoprotein E receptor 2 (apoER2)-dependent signaling in endothelial cells and in placental trophoblasts that ultimately promotes thrombosis and fetal loss, respectively.

Genetic variants of ApoE and ApoER2 differentially modulate endothelial function.

It is poorly understood why there is greater cardiovascular disease risk associated with the apolipoprotein E4 (apoE) allele vs. apoE3, and also greater risk with the LRP8/apolipoprotein E receptor 2 (ApoER2) variant ApoER2-R952Q. Little is known about the function of the apoE-ApoER2 tandem outside of the central nervous system.

Proliferating effect of orotic acid through mTORC1 activation mediated by negative regulation of AMPK in SK-Hep1 hepatocellular carcinoma cells.

Orotic acid (OA) is a tumor promoter of experimental liver carcinogenesis initiated by DNA reactive carcinogens, the molecular mechanisms of which have not been fully elucidated. OA increases cell proliferation and decreases apoptosis in serum-starved SK-Hep1 hepatocellular carcinoma cells, which may ascribe to the inhibition of AMP-activated protein kinase (AMPK) phosphorylation and thus activation of mammalian target of rapamycin complex 1 (mTORC1). The effects of OA on mTORC1 activation, cell proliferation, and cell-cycle progression to S and G2/M phases were completely reversed by rapamycin.

Role of the AMPK/SREBP-1 pathway in the development of orotic acid-induced fatty liver.

Orotic acid (OA), an intermediate in pyrimidine metabolism, has been used for a variety of purposes, such as dietary supplements. Although it is well documented that OA induces fatty liver in a species-specific manner, the precise molecular mechanisms remain unclear. The present study investigated the role of the adenosine monophosphate-activated protein kinase (AMPK)-sterol regulatory element-binding protein-1 (SREBP-1) pathway in the OA-induced fatty liver.