Circulation research
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Circulation research · Mar 2012
Homocysteine upregulates soluble epoxide hydrolase in vascular endothelium in vitro and in vivo.
Hyperhomocysteinemia is a risk factor of atherogenesis. Soluble epoxide hydrolase (sEH) is a major enzyme that hydrolyzes epoxyeicosatrienoic acids and attenuates their cardiovascular protective effects. Whether homocysteine (Hcy) regulates sEH and the underlying mechanism remains elusive. ⋯ ATF6 activation and DNA demethylation may coordinately contribute to Hcy-induced sEH expression and endothelial activation. Inhibition of sEH may be a therapeutic approach for treating Hcy-induced cardiovascular diseases.
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Circulation research · Mar 2012
High levels of costimulatory receptors OX40 and 4-1BB characterize CD4+CD28null T cells in patients with acute coronary syndrome.
Patients with acute coronary syndrome (ACS) predisposed to recurrent coronary events have an expansion of a distinctive T-cell subset, the CD4(+)CD28(null) T cells. These cells are highly inflammatory and cytotoxic in spite of lacking the costimulatory receptor CD28, which is crucial for optimal T cell function. The mechanisms that govern CD4(+)CD28(null) T cell function are unknown. ⋯ Costimulatory pathways are altered in CD4(+)CD28(null) T cells in ACS. We show that the inflammatory and cytotoxic function of CD4(+)CD28(null) T cells can be inhibited by blocking OX40 and 4-1BB costimulatory receptors. Modulation of costimulatory receptors may allow specific targeting of this cell subset and may improve the survival of ACS patients.