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Study On The Mechanism Of Endothelial Cell Injury And Apoptosis Induced By Trans Fatty Acids

Posted on:2012-05-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:B QiuFull Text:PDF
GTID:1111330368995432Subject:Food Science and Engineering
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Trans fatty acids (TFA) is a common constituent of lipids and oil food. Though the realationships between TFA and cardiovascular diseases have been reported, the mechanism of TFA effecting on cardiovascular remains unknown. Endothelial injury is the initial stage of atherosclerosis and othe cardiovascular diseases, endothelial injury play an important role in the progress of cardiovascular. Besides, endothelial apoptosis which is an early factor causing endothelial injury, plays an significant role in the early stage of cardiovascular.At present, the effects of TFA on atherosclerosis and othe cardiovascular diseases at home and abroard mainly focus on endothelial cell injury and endothelial cell apoptosis two aspects. Most foreign researchers treating the mixture of TFA as an research subject study the effect of TFA on the coronary heart disease and brachial artery endothelial function. There are few reports about the effects of different saturation of TFA(9t C18:1,9t,12t C18:2) on the cardiovascular diseases and brachial artery endothel ial function. The were little research of the realationship between TFA and human health in spite of the TFA content of chinese food rising year after year. At present in the fields of domestic research is still in its beginning stage. There were little conculted literature review limitting to the relationship of TFA and huamn health.The research subject aiming at different saturation of TFA(9t C18:1; 9t,12t C18:2) were executed to study the relation of TFA and atherosclerosis. The mechanism of TFA on endothelial cells mainly involved endothelial injury and endothelial apoptosis two aspects. The study of the effects of TFA on the endothelial cells was of an important theoretical and social value, and provides theoretical basis and reliable scientific data for the prevention and treatment of cardiovascular diseases.The results are showed as followed:1. TFA at different saturation (9t C18:1,9t,12t C18:2) could inhibit the cell viability, and induced cells take place an significant morphological change. At last, cells showed an typical apoptosis status. 2. TFA induced the amount of LDH leak rise, inhibited the SOD vitality and depressed the cellular radical scavenging ability, and then increased the cellular lipid metabolism product-MDA. Above indexes showed that TFA can induce endothelial cells injury.3. LNAME cultured with TFA decreased the viability of HUVEC. When SNP cocultured with TFA, the viability of HUVEC rised. The secretory volume of NO, the activity and mRNA expression of eNOS declined, but the and mRNA expression of iNOS had no significant difference with the control group when HUVEC cultured with TFA. The evidence enableed us to conclude that TFA could reduce the secretory volume of NO through depressing the activity of eNOS. It suggested that NOS-NO system is one of the mechanisms participating in the course of TFA inducing HUVEC injury.4. The mRNA level of VCAM-1, ICAM-1 and E-selectin rised significantly after HUVEC treated with 9t C18:l and 9t,12t C18:2, it means that TFA could induce HUVEC injury through rising the mRNA expression of adhesion molecule.5. Endothelial apoptosis could be observed through confocal laser scanning microscope and flow cytometry after treated with TFA. In the apoptosis course, activities and mRNA expression of caspase-3,-8,-9 rised. Both z-IETD-fmk and z-LEHD-fmk completely prevented TFA-induced activation of caspase-3, and z-IETD-fmk could blocked activation of caspase-9 completely. The activation of caspase-3 and -9 by TFA was inhibited by z-IETD-fmk, a caspase-8 inhibitor, suggesting that caspase-9 might be activated through a mitochondrial pathway depending on Bid activation, which is downstream of TFA-activated caspase-8. The research of the effects of TFA on the endothelial cells supplied an scientific evidence, and provided theoretical basis for the mechanism of cardiovascular diseases.From the above results, it can be concluded that TFA induce endothelial cell injury through NOS-NO system; and TFA aggravate the endothelial cell injury through rising the mRNA expression of VCAM-1, ICAM-1 and E-selectin; TFA induce endothelial cell apoptosis through activating the death receptor pathway and the mitochondrial pathway.
Keywords/Search Tags:trans fatty acids, human umbilical vein endothelial cells, endothelial injury, NOS-NO system, apoptosis, caspase, adhesion molecules
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