Study On Signal Transductions Of Endothelial Cell Injury And Proliferation

Endothelial cell (EC) abnormality is the initial event of cardiovascular diseases.Exploring signal transductions in abnormal endothelial cells is very helpful ofenriching our knowledge about several kinds of cardiovascular diseases and also inresearching effective mechanisms of drugs. in this paper, our mainly tasks are asfollows:We established an injury model of H2O2 induced ECs and 50% ECs died afterthat. Ferulic acid (FA) protected ECs against this damage effect and the cell viabilitywas as high as 90% of the control cells. Griess assay was employed to detect theproduction of nitrix oxide (NO), which was overproducted when induced by H2O2 andalso could be suppressed by pretreated with FA. H2O2 stimulated the activation ofMAPKs (ERK, JNK and p38), iNOS and ICAM-1, meanwhile decreased eNOSexpression. And all these effects could be inhibited by FA. Then we established a proliferation model of lipopolysaccharide (LPS) inducedECs. We found that LPS increased the DNA synthesis and cell number, and alsocaused cells from G1 to S progress. What's more, it stimulated the phosphorylation ofERK and p38, not JNK and increased the expression of ICAM-1 and iNOS not eNOS.Then we used inhibitors of ERK (PD98059), p38 (SB202190), NOS (L-NAME),PI3K (LY294002) and donor of NO (SNP) to study on the relations among signals.PD98059, L-NAME and LY294002 inhibited LPS induced cell proliferation byincrease the population of G1/G0 cells. SB202190 and SNP promoted the cellproliferation by causing cells from G1 to S progress. SB202190 promoted ERKactivation, LY294002 and L-NAME inhibited iNOS and ICAM-1 expressionrespectively. All these results indicated:1. LPS activated ERK and p38, and p38 negatively regulated the activation ofERK, which was in charge of the cell proliferation;2. PI3K activation up-regulate iNOS expression and NO production,iNOSactivation up-regulate ICAM-1 expression;3. MAPK pathway and PI3K pathway were independent of each other.