Effect Of Glucocorticoid On The Stability Of Carotid Plaque

Background: Carotid artery stenosis is usually refers to the effect of multiple factors,such as inflammatory cells,lipid accumulation in the carotid artery intima-media thickening so that a disease of carotid artery lumen diameter became narrow.Carotid plaque formation is the main pathological process.Its onset is slow,difficult to detect,often occurs before clinical symptoms,if not timely treatment may cause serious complications of stroke,paralysis or even death.Carotid artery plaque can be divided into stable plaque and unstable plaque according to the feature of structure.For the patients with stenosis of carotid artery plaque instability caused more serious complications.Stress is an important factor affecting the development of vascular disease,glucocorticoids is the hub of the stress response.Regulate sugar biosynthesis of fat,and protein,but also has development,immune response,as well as regulating the nervous system activity to suppress the immune response,anti-inflammatory,anti-drug,anti-shock effect,involved in metabolism,growth and other cardiovascular function physiological and pathological processes.Studies have found high concentrations of cortisol in humans and expression of glucocorticoid receptor can cause high blood pressure,high blood sugar,high cholesterol and other cardiovascular risk factors.The excessive release of glucocorticoids on the occurrence of atherosclerosis and development has an impact.So,whether there are differences in the level of glucocorticoid in patients with stable plaque of carotid artery stenosis and unstable plaque of carotid artery stenosis patients? Whether two plaques in the presence of glucocorticoid receptor expression differences or not.Glucocorticoid has a control on how the stability of carotid plaque.Clarify the role of glucocorticoids in the regulation of carotid plaque stability mechanism to provide new biomarkers and targets for intervention to assess the progression of carotid stenosis,for the early diagnosis and prevention of disease,condition assessment and comprehensive treatment has significance.Objective: Investigation on Instabilities of carotid plaque in patients with carotid artery stenosis and stability of carotid plaque in patients with carotid stenosis blood glucocorticoid levels and plaque in the presence or absence of glucocorticoid receptor expression differences,suggesting that glucocorticoids and by body in carotid plaque stability may play a role.Effect through animal experiments glucocorticoids on carotid plaque stability,a clear increase in glucocorticoid levels is the body under stress conditions in a protective factor,or caused damage of plaque instability factors.Provide the basis for the next step of the mechanism of glucocorticoid regulation of carotid plaque stability.Methods: Clinical study: Vascular January 2013-March 2015 period in Shanghai Changhai Hospital surgical intends carotid stenosis carotid endarterectomy treatment selection based on the group conditions of patients admitted to hospital the next day 8:00 fasting peripheral venous blood collection 4 ml,plaques obtained from carotid endarterectomy surgery.Measured by radioimmunoassay bleeding in glucocorticoid levels.After the plaque made of paraffin-embedded sections,hematoxylin-eosin and Sirius red staining,according to the plaque staining plaque set into instability and unstable plaque group were compared glucocorticoid hormone levels,and then the two plaque macrophages and glucocorticoid receptor immunohistochemical staining,whether the difference in expression between the two groups.Animal experiment: To 6-week-old Apo E-/-mouse line adrenalectomy fed a high-fat diet and normal saline,two weeks after the body of glucocorticoid depletion and recover from trauma,building stenosis model mice were randomly divided into 3 group,and were given the stress-dose glucocorticoids(5 mg / kg / d),physiological doses of corticosteroids(0.5 mg / kg / d),solvent control intervention,six weeks after the mice were sacrificed,with collection of small rat blood about 1ml,respectively serum glucocorticoid,IL-6,hs-CRP and compared.Mouse carotid artery dissection,embedded in paraffin.Hematoxylin-eosin staining,Sirius red staining of collagen fibers by comparing carotid plaque lipid plaque area occupied by percentage and thus relatively stable fibrous cap thickness of plaque in each group.On the carotid plaque stability understand the different doses of glucocorticoids.In P <0.05 indicates statistical significance.Result: Clinical results of samples: The amount of the sample group of 52 cases,grouped according to HE and Sirius red staining,unstable plaque group 35 cases,17 cases of unstable plaque group.Two groups of patients were glucocorticoids(13.45 ± 2.74 ug / dl vs 11.74 ± 2.19 ug / dl,P <0.05),the difference was statistically significant.The two groups were positive macrophages in plaque index(34.06 ± 7.55% vs 25.11 ± 7.16%,P <0.01),the glucocorticoid receptor positive index was(20.77 ± 5.62% vs 12.62 ± 3.19%,P <0.001),the differences were statistically significant.Animal experiment results: To the end of the experiment,each of the remaining eight mice.Carotid plaques HE and Sirius red staining,measurement and analysis by computer software.Stress-dose group,physiological dose group,the percentage of plaque area in the control group of collagen fibers were 2.09 ± 0.32%,3.73 ± 0.58%,2.69 ± 0.37%,compared with each other differences were statistically significant(P each between the two groups <0.01);the percentage of lipid plaque area was 4.76 ± 0.56%,2.21 ± 0.30%,3.30 ± 0.37%,compared with each other differences were statistically significant(P <0.01)between each of the two groups;fibrous cap thickness were 47.0 ± 3.6 um,64.6 ± 4.1 um,56.1 ± 2.2 um,mutual differences were statistically significant(P <0.01)between the two groups each.Serum corticosteroids were 18.50 ± 4.68 ug / dl,5.38 ± 1.86 ug / dl,0,consistent with the mice under stress and physiological state level.IL-6 was 2.18 ± 0.84 pg / ml,5.09 ± 1.19 ug / dl,6.65 ± 1.02 ug / dl;hs-CRP were 0.62 ± 0.24 mg / dl,1.38 ± 0.43 mg / dl,1.84 ± 0.26 mg / dl,inflammatory cytokines with glucocorticoids increases.Conclusion: Clinical studies of plaque instability and glucocorticoid receptor higher than the stability of plaque group,indicating serum glucocorticoid and plaques glucocorticoid receptor and carotid plaque stability related.In animal studies,plaque stability three groups of mice were physiological dose group> control group> stress-dose group.In addition to the impact of endogenous glucocorticoids,sustained high glucocorticoid levels may lead to disorders of carotid artery endothelial function,and damage the structure and function of the wall,and enhance vascular smooth muscle contraction,so that stenosis,local blood hemodynamic changes,shear wall should change.These can lead to carotid atherosclerotic plaque destabilization,thereby affecting the progress and outcome of carotid stenosis.The physiological doses of glucocorticoids may inhibit inflammation leaving the plaques more stable.So,long-term glucocorticoid stress levels can lead to plaque instability.However,the specific impact of the mechanism needs further experiments in vitro cell and molecular study.