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Explore The Role Of LncRNA Morrbid In Vascular Calcification

Posted on:2020-04-18Degree:MasterType:Thesis
Country:ChinaCandidate:W Z HongFull Text:PDF
GTID:2404330611964955Subject:Clinical Medicine
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Cardiovascular disease is the number one cause of death worldwide: more people die of cardiovascular disease each year than any other cause of death.According to the World Health Organization,in 2016,an estimated 17.9 million people died of cardiovascular disease,accounting for 31% of the total number of deaths worldwide.Of these,85% died of heart disease and stroke.More than three-quarters of cardiovascular deaths occur in low-and middle-income countries.Of the 17 million under 70 deaths caused by noncommunicable diseases,82% are in low-and middle-income countries and 37% are caused by cardiovascular disease.Vascular calcification,that is,deposition of calcium phosphate in the arterial wall,the pathophysiological process often manifests as stiff blood vessel wall,reduced elasticity of the blood vessel wall,thrombosis,vascular rupture,cerebral hemorrhage,cerebral infarction,myocardial infarction and other cardiovascular diseases.An important factor in the high incidence of vascular disease and high mortality.Approximately 60% of people over the age of 60 and 80% of those over the age of 80 have been considered to be unregulated end-stage degenerative diseases.With the deepening of the research,it is found that vascular calcification is an active regulation process,which is dynamically changing during the development of atherosclerosis.It can be expressed as stable plaque and also a sign of inflammation.Clinical vascular calcification is an important predictor of death and disability of cardiovascular and cerebrovascular diseases.Not only is the incidence high,but there are huge challenges in treatment,especially the problem of interventional therapy,which is often excluded from clinical research.Therefore,a series of studies on vascular calcification from basic to clinical have important theoretical and practical significance.LncRNA was originally thought to be the "noise" of genomic transcription,a by-product of RNA polymerase II transcription,and has no biological function.However,literature studies have shown that lnc RNA is involved in many important regulatory processes such as X-chromosome silencing,genomic imprinting,chromatin modification,transcriptional activation,transcriptional interference,and intranuclear transport.These regulatory effects of lnc RNA have also begun to attract widespread attention.Lnc RNA morrbid was first published in 2016 by the American Academy of Sciences in Nature.Neutrophils,eosinophils,and "classical" monocytes add up to about 70% of the total white blood cells in the body and are the shortest-lived cells in the human body.But their responsiveness can sometimes be very strong and can even damage healthy tissue around them.Studies have shown that Lnc RNAMorrbid regulates the transcription of Bcl2l11 and promotes the accumulation of PRC2 complex in the promoter of the adjacent Bcl2l11 apoptotic gene,thereby controlling the life of inflammatory cells such as neutrophils.At present,there are only 6 articles about lnc RNA morrbid,mainly focusing on immunity.And no studies have elucidated the relationship between lnc RNA morrbid and calcification.As an important risk factor and deterioration condition of cardiovascular disease,calcification requires further research.Objective: To investigate the role of Lnc RNA Morrbid in vascular calcificationmethod:1.Explore the establishment of calcification model(1)Movas cells were treated for different time and calcification conditions,and alizarin red staining was used to detect the degree of calcification.(2)Murine primary smooth muscle cell calcification,alizarin red staining,calciumion quantification,q PCR assay to detect calcification.(3)Drug treatment of C57 mice established a calcification model of living mice,alizarin red staining,calcium ion quantification,and q PCR assay to detect the degree of calcification.(4)The human abdominal aorta tissue sample was stained with alizarin red to detect the degree of calcification.2.Expression of Lnc RNA Morrbid in calcification(1)Detection of Lnc RNA Morrbid expression in mouse primary smooth muscle cells and C57 mouse tissue samples(2)Detection of Lnc RNA Morrbid expression by q PCR in human abdominal aorta tissue samples3.Down-regulation of Lnc RNA Morrbid and its effect on calcification(1)Using different si RNAs to detect their knockdown efficiency.The most efficient si RNA was selected for knockdown experiments.(2)Calcification of mouse primary smooth muscle cells,observation of the effect of silencing Lnc RNA Morrbid on calcification.4.The mechanism of action of Lnc RNA Morrbid(1)RNA-seq looks for regulatory pathways that Lrc RNA Morrbid may be involved in and downstream.(2)FISH experiments to locate the distribution of Lnc RNA Morrbid.result:1.Successfully established movas,mouse primary smooth muscle cells,C57 live mousecalcification model,and human basal aortic aneurysm tissue samples were calcified.2.LncRNA Morrbid increased expression in calcification models and human tissue samples.3.After inhibition of Lnc RNA Morrbid,calcification is significantly alleviated4.The experimental results show that Lnc RNA Morrbid is localized in the cytoplasm and regulates the post-transcriptional modification process.in conclusion:In summary,the evidence from our study preliminarily elucidates the role of lnc RNA Morrbid in vascular calcification and provides new insights into the use of lnc RNA for the diagnosis and treatment of vascular calcification.
Keywords/Search Tags:vascular calcification, lncRNA, calcification, atherosclerosis
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