Caspase-1 Inflammasome Activation Mediates Homocysteine-Induced Pyrop-Apoptosis in Endothelial Cells.

ABSTRACT:

Rationale

Endothelial injury is an initial mechanism mediating cardiovascular disease.

Objective

Here, we investigated the effect of hyperhomocysteinemia on programed cell death in endothelial cells (EC).

Methods and results

We established a novel flow-cytometric gating method to define pyrotosis (Annexin V(-)/Propidium iodide(+)). In cultured human EC, we found that: (1) homocysteine and lipopolysaccharide individually and synergistically induced inflammatory pyroptotic and noninflammatory apoptotic cell death; (2) homocysteine/lipopolysaccharide induced caspase-1 activation before caspase-8, caspase-9, and caspase-3 activations; (3) caspase-1/caspase-3 inhibitors rescued homocysteine/lipopolysaccharide-induced pyroptosis/apoptosis, but caspase-8/caspase-9 inhibitors

SUBMITTER: Xi H 

PROVIDER: S-EPMC4867131 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature