The Mechanism Of SO₂ Induces Vascular Relaxation Through PI3K/Akt/eNOS Signaling Pathway

In recent years,environmental pollution has been one of the hot topics that people have paid attention to,threatening the health of all human beings.As the most common exogenous air pollutant,sulfur dioxide?SO₂?is the culprit leading to air pollution,causing people's extensive attention.A large number of epidemiological studies at home and abroad have shown that SO₂ is closely related to the occurrence and development of cardiovascular disease.In addition,some research reports indicate that SO₂ can cause vasodilation as a gas signal molecule,but the related signal pathways involved are unclear.Therefore,it is of great significance to study the underlying mechanism of SO₂ induced vasodilation,which can provide more experimental evidence for cardiovascular diseases caused by SO₂.In this study,we first used an isolated vascular ring experiment technique to apply different concentrations of SO₂?30?M,300?M,1500?M?to aortic vessels in the endothelium intact and deendothelial groups,and added inhibitors LY294002 or L-NAME to them.,observe and record the effect of SO₂ on vascular ring tension,and found that,in the endothelium intact group,the blocking agents LY294002 and L-NAME have a partial inhibitory effect on SO₂ relaxing of blood vessels,suggesting that SO₂ may mediate PI3K/Akt/eNOS signaling pathway to induce vasodilation.Second,in order to further explore the mechanism of SO₂vasodilation,the quantitative expression of PI3K mRNA and Akt,eNOS,p-Akt,and p-eNOS protein expression level and NO content,NOS enzyme activity,cAMP and cGMP content,were measured using real-time PCR,Western Blot,NO,NOS kit,cAMP,and cGMP ELISA kits,respectively.The results showed that when the SO₂ concentration was 30?M,the expression levels of PI3K,p-Akt,and p-eNOS proteins were significantly increased,and when the SO₂ concentration was 300?M or 1500?M,the PI3K,p-Akt,and p-eNOS protein levels were significantly reduced and NOS activity,NO,cGMP activity were significantly increased.The results indicate that the mechanism of SO₂induced vasodilation may involve PI3K/Akt/eNOS signaling pathways in endothelial cells.In addition,the changes in the activity of caspase-3and caspase-9 by SO₂ were also studied.As a result,it was found that SO₂ at high concentrations increased the activity of caspase-3 and caspase-9.It shows that high concentration of SO₂ will cause certain damage to vascular tissues.In order to further study the effect of SO₂ on the PI3K/Akt/eNOS signaling pathway,high-throughput sequencing of the transcriptome was performed at the cellular level.Data analysis revealed that SO₂ had a total of 16 on the PI3K/Akt/eNOS signaling pathway of human arterial vascular smooth muscle cells.12 differentially expressed genes,12 of which are up-regulated genes,which are IL7R,IGF1,FGF18,IFNAR2,EREG,LPAR2,MTCP1,IL6,CSF3,AREG,THBS4,EFNA1,and 4 are down-regulated genes,which are KIT,CHRM2,PDGFB,PGF,and these genes are involved in biological processes such as immune response,cell proliferation,and inflammatory response.In summary,SO₂ may cause vasodilation in rat aorta by mediating PI3K/Akt/eNOS signaling pathways.High concentrations of SO₂ can cause damage to vascular tissue.In addition,based on transcriptome sequencing technology,16 differentially expressed genes of PI3K/Akt/eNOS signal pathway in aortic vascular smooth muscle cells were obtained by SO₂,providing a new direction for our next research.