Correlation Between PCSK9 And The Mechanism Of Mitral Valve Calcification In Senile Calcified Valvular Heart Disease

Objective: Senile calcified valvular heart disease(SCVD)is a disease that seriously harms human health.It is mainly characterized by degenerative disease,thickening,fibrosis and calcification of valve connective tissue.With the extension of human lifespan,the disease has become an independent heart disease that affects and threatens the health of the elderly.SCVD patients can have calcification on all four heart valves,but the clinical manifestation is mainly calcified aortic valve disease(CAVD),accounting for about 85% of SCVD patients;the secondary manifestation is mitral valve calcification(Mitral valve calcification,MVC),accounting for about 15% of patients.The histopathological examination of the patients by the researchers showed that SCVD has the characteristics of lipid infiltration,inflammation and calcification.The current mechanism research mainly focuses on CAVD.However,the researchers found that there are differences in the pathogenesis of CAVD and MVC.Human proprotein convertase Subtilisin/kexin type 9,PCSK9 plays a major role in lipid metabolism,inflammation and apoptosis.The current research proves that PCSK9 is related to the occurrence of CAVD.However,it is still unclear whether PCSK9 is related to mitral valve calcification in SCVD,and the specific mechanism of PCSK9 in valve calcification has also been discovered.In this study,we will speculate the role of PCSK9 in the pathogenesis of mitral valve calcification by exploring the expression levels of PCSK9 and the classic inflammatory pathway TLR4/NF-κB pathway in mitral valve calcification patients.Methods:This study screened 20 patients with mitral valve calcification from March 2018 to December 2019 in the First Hospital of Guangxi Medical University as the experimental group,and 12 patients with mitral valve prolapse as the control group.The two groups of patients confirmed whether the patients’ mitral valve was calcified by echocardiography and computed tomography(Computed Tomographyaphy,CT),and were marked as MVC group(experimental group)and control group.The biochemical analyzer was used to detect the risk indicators related to valve calcification,including total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol(HDL-C),triglyceride(TG),apolipoprotein A1(Apo A1)and apolipoprotein B(Apo B),lipoprotein(a),[Lp(a)] and blood glucose(BS)level,using Western Blot(WB)and Quantitative Real-time PCR,(q RT-PCR)analysis of PCSK9 in the mitral valve leaflet tissues of different groups,TLR4 and NF-κB expression levels.Finally,the blood lipid profile and the expression differences of mitral valve PCSK9,TLR4,and NF-κB were analyzed to analyze the relationship between them and mitral valve calcification.Results: The plasma Lp(a)levels in the two groups were significantly different(p<0.05),and the total Lp(a)level in patients with MVC was higher than that in the control group.At the same time,there was no significant difference in TC,LDL-C,Apo B,TG,HDL-C,Apo A1 and fasting blood glucose between the two groups(p> 0.05).WB and q RT-PCR verified that the expression levels of PCSK9,TLR4 and NF-κB in mitral valve tissues of MVC group were higher than those of control group,the difference was statistically significant(P<0.05).Conclusion:(1)The PCSK9 and TLR4/NF-κB pathways are highly expressed in mitral valve calcification in elderly calcific heart disease,and PCSK9 is related to the pathway,suggesting that PCSK9 may regulate the pathological process of mitral valve calcification through the TLR4/NF-κB pathway.(2)Lp(a)is related to mitral valve calcification in elderly calcified heart disease,and may be a risk factor for mitral valve calcification.