The Study On The Potential Mechanism Of Lipid Level In The Development And Rupture Of Abdominal Aortic Aneurysm

Background:Abdominal aortic aneurysm is a common and serious disease that threatens people's health.Once it occurs,it will gradually expand until it breaks.Therefore,it is particularly important to monitor the development and changes of the aneurysm.The autopsy results show that the diameter of aneurysm is an important determinant of rupture,and the risk of rapture increases greatly as aneurysm diameter increasing.Making a decision of surgery or follow-up basing on the maximum diameter of the aneurysm is the most common practice at present.Current consensus shows that:when the anexurysm diameter is less than 4 cm the risk of rupture is low,follow-up with regular ultrasound monitoring,when the aneurysm diameter is up to 5.4 cm,the recommended surgery is necessary.There is controversy when the aneurysm diameter is between 4.0-5.4 cm,if it is suitable for endovascular treatment,surgery immediately or continue follow-up can be chosen;if the aneurysm diameter of over 5.4 cm,or the growth of diameter of the aneurysm increase quickly(greater than lcm/year),should be underwent elective surgery.There are still nearly 13%of the proportion of rupture in patients with abdominal aortic aneurysm diameter less than 5cm.Therefore,the standard to determine of treatment plan according to the largest diameter of the aneurysm is obviously not suitable for all patients with abdominal aortic aneurysm.To choose conservative or surgical treatment,depends on relationship of the rapture risk of aneurysm,surgical mortality,and life expectancy.Therefore,in addition to the largest diameter of the aneurysm,it is necessary to explore other risk factors associated with the largest diameter of the aneurysm,which is beneficial to the comprehensive evaluation of the risk of development and rupture of abdominal aortic aneurysm.The epidemiological investigation shows that the abnormal lipid metabolism is one of the most important risk factors for the occurrence and development of atherosclerosis.Atherosclerosis is the most common cause of abdominal aortic aneurysm,accounting for more than 95%of all cases.Many studies have shown that arterial stiflfness is a common manifestation of abdominal aortic aneurysm wall.Lipid metabolism is associated with the development of abdominal aortic aneurysm,an important evidence came from the histological found that aortic wall thickening was associated with deposition of cholesterol crystallization in the Endometrial fibrous tissue.Studies have shown that cholesterol and lipid metabolism involved in the formation of abdominal aortic aneurysm,but the exact molecular mechanism is not clear.Studies found that in the course of vascular endothelial damage and atherosclerosis which caused by abnormal blood lipid,the inflammatory reaction was throughout.On one hand,some of the lipoproteins themselves can induce inflammatory reaction,e.g,LDL can promote endothelial cells to produce IL-6 and TNF-? and other inflammatory factors,the vascular endothelial injury and the formation of atherosclerosis can be induced by the inflammatory response.On the other hand,the inflammatory response can also cause or aggravate the disorder of blood lipid metabolism.Inflammatory factors,such as IL-6,TNF-a and IL-1?,can lead to increased plasma levels of TG and VLDL,the possible mechanism is synthesis of endogenous VLDL,TG,and inhibition of the activity of lipoprotein lipase caused by inflammatory factors.The formation and development of abdominal aortic aneurysm are associated with abnormal blood lipid,atherosclerosis,and inflammation.abnormal blood lipid can lead to atherosclerosis,involved in the formation of abdominal aortic aneurysm,induce inflammation,meanwhile inflammation can aggravate the disorder of lipid metabolism and play an important role in the formation of abdominal aortic aneurysm.AAA is considered to be a chronic inflammatory disease,it is mainly origin from the arterial wall inflammation.Therefore,the role of abnormal blood lipid and inflammatory reaction in the occurrence and development of abdominal aortic aneurysm is worth to be further discussed.Transient vanilla aldehyde Receptor Potential Vanilloid l(TRPV1),is a nonspecific cation channel is highly selective excited capsaicin receptor,its role in cardiovascular metabolic diseases have been reported.It can be activated by endogenous and exogenous substances such as capsaicin,high temperature,proton,lipid metabolism etc.studies show that TRPV1 are involved in regulating lipid and vascular function regulation,inflammatory reaction and adipose differentiation,and is closely related to arteriosclerosis,lipid metabolism.We hypothesized that TRPV1 may play a role in the formation and development of abdominal aortic aneurysm,but the expression of TRPV1 in human abdominal aortic aneurysm wall has not been reported.Calmodulin(CaM)is an acidic protein which will not increase until intracellular free calcium levels increase,so it reflects the intracellular calcium concentration.When TRPV1 is activated,the intracellular flow of Ca2+ increased,the expression of CaM increased,they are closely related.PPAR ? is a subtype of peroxisome proliferator activated receptor of PPAR,is a kind of key transcription factor of nutrient metabolism and energy homeostasis,predominantly control the balance of lipid metabolism and energy of adipose tissue and skeletal muscle cells.In a abdominal aortic aneurysm of rat model,it was found that when PPAR(a genes related to lipid metabolism which exist in vascular smooth muscle)loss,it can promote the development of abdominal aortic aneurysm.At present,there is no report about the expression and role of PPAR in human abdominal aortic aneurysm.Blood lipid abnormalities lead to vascular endothelial injury,and inflammatory response in turn to each other.There are many researches about IL-6^ TNF-a?VCAM-1?MCP-1,and have been confirmed that they are closely associated with the genesis and development of AAA,but their differentias in different abdominal aortic aneurysm sizes,and expression under different conditions are rarely reported,and whether it is associated with blood lipid abnormalities also worth exploring.So in our study we speculated that blood lipid abnormalities plays an important role in the occurrence and development of abdominal aortic aneurysm.Its mechanism may be associated with the blood lipid metabolism,inflammatory factors and inflammatory reaction.Objective:To approach the different blood lipid levels in different size of the abdominal aortic aneurysm patients,to approach whether there are differences in TRPV1,CaM,PPAR Sexpressions which associated with lipid metabolism.To inspect IL-6,TNF-a,VCAM-1,and MCP-1 expressions in patients with different size of abdominal aortic aneurysm,and to approach their relationships with blood lipid levels.Methods:Retrospective analysis of the clinical data of 296 cases of abdominal aortic aneurysm,the patients were divided into three groups according to the maximum diameter:group A:3 cm ? maximum diameter<4 cm;group B:4 cm?maximum diameter<5.4 cm;group C:maximum diameter>5.4 cm.Analysis the sex,smoking history,drinking history,history of diabetes,hypertension,peripheral atherosclerosis,aneurysm size,rupture,glycerin three fat,cholesterol,high density lipoprotein,low density lipoprotein,apolipoprotein A,serum creatinine,hemoglobin,white blood cell count,platelet count,fibrinogen platelet,and cardiac troponin T in the three groups,compare their differences.A total of 40 cases with wall tissue of abdominal aortic aneurysm were collected,they were divided into four groups according to the maximum diameter:group A:3 cm ? maximum diameter<5 cm,unruptured;group B:maximum diameter>5 cm,unruptured;group C:3 cm ?maximum diameter<5 cm ruptured,group D:maximum diameter>5 cm ruptured.Patients' TC,TG,and LDL in the four were compared.The expression of TRPV1,CaM and PPAR in the four groups was tested by immunohistochemistry and compared among groups.The abdominal aortic aneurysm wall tissue specimens were collected,they were divided into four groups according to the maximum diameter:group A:3 cm<maximum diameter<5 cm,unraptured;group B:maximum diameter>5 cm,unruptured;group C:3 cmv maximum diameter<5 cm ruptured,group D:maximum diameter>5 cm ruptured.The expression of TRPV1,CaM and PPARSin the four groups were tested by PCR technique.The blood samples of patients with abdominal aortic aneurysm were collected,they were divided into four groups according to the maximum diameter:group A:3 cm? maximum diameter<5 cm,unruptured;group B:maximum diameter>5 cm,unruptured;group C:3 cm?maximum diameter<5 cm ruptured,group D:maximum diameter>5 cm ruptured.The IL-6,TNF-?,VCAM-1 and MCP-1 of the four groups were tested by ELISA technology.Results:1.There were differences in gender,rupture rate,low density lipoprotein,triglyceride,total cholesterol,lipoprotein among the three groups.The numerical perspective showed that the greater the diameter of aneurysm,the proportion of patients with hyperlipidemia was higher,and more easily to rupture.2.The distribution trend of TG,TC,and LDL in four groups were consistent,blood lipid levels were higher in group B and group D when compared with group A and group C.In the large diameter groups(group B and group D),the TG level in ruptured group(group D)was higher than that of unruptured group(group B).In the groups with small diameter,the TC level in ruptured group was higher than that of unrupture group.3.In the four groups,TRPV1,CaM in large diameter groups were higher than small diameter groups,when compared between the unruptured groups.In the same diameter groups the expression of TRPV1,CaM in ruptured groups were higher than unruptured groups.There was no difference in TRPV1 and CaM between the two ruptured groups.The expression of PPAR?in the small diameter and unruptured group was higher than that in the larger diameter and ruptured group.4.In the four groups,the IL-6,TNF-,VCAM-1,MCP-1 were higher in large diameter groups.And the inflammatory factors in ruptured groups were higher than that in the unruptured groups.Conclusion:1.The proportion of hyperlipidemia is different in different diameter patients,the larger of the size of the abdominal aortic aneurysm,the more patients with hyperlipidemia.2.There are differences in the expression of TRPV1?CaM?PPAR? which related to lipid metabolism in patients who with different size of the abdominal aortic aneurysm,and the distribution trend of blood lipid of the same with TRPV1,CaM,opposite with PPAR?.3.The IL-6,TNF-?,VCAM-1,MCP-1 levels in large diameter groups are higher than that in small diameter groups.In the same diameter groups the IL-6,TNF-?,VCAM-1,MCP-1 levels the ruptured group is higher,the performance trends are in accord with the blood lipid levels.