| Both basic and clinical studies have confirmed that inflammatory response plays an important role in the occurrence and development of atherosclerosis(AS) as well as its caused clinical events.As the most important antigen-presenting cells activating T lymphocytes,dendritic cells(DCs) have the important functions of determining T lymphocytes activation,apoptosis,and aggregation.DCs and macrophage,another cells have the function of antigen-presenting,all originate from bone marrow hematopoietic stem cells.DCs can be found in many human organs and tissues,although all these DCs have the function of antigen-presenting,their specific manner of in action display a marked difference.DCs can be devided into different subset according the molecule markers expressing in the surface.Macrophage more skilful playing a role as a "scavenger" clean out the foreign substance invade into the body compare with the function of antigen-presenting.Different from macrophage,DCs can feel minute change in internal environment in the body,provided with powerful function of activate the infantility T lymphocytes,is professional antigen-presenting cells.In1967, Mosier etal.found there need an "assistant cell" between antigen and T/B lymphocytes to activate the T/B lymphocytes,and called its as "message transmitter".Now we know,DCs,macrophage and some B lymphocytes all have the function of antigen-presenting,as the most important antigen-presenting cells which transport the antigen to the T lymphocytes,DCs is called as the professional antigen-presenting cells.In summary,the DCs,s function of antigen-presenting is first capture foreign substance in periphery of body,then immigrate to periphery lymph nodes,and at last present the antigen to the T lymphocytes in the manner of antigen peptide-MHC molecular complex,to activate the immaturity T lymphocytes to mature T lymphocytes which have specific activity to the antigen the DCs presented.During the process of maturation,often associated with their migration to lymphoid organs,DCs shift from an antigen-capturing mode to a T cell sensitizing mode.At the end of the process,they are located in the T cell zone display antigenic and costimulatory signals required for optimal activation of T lymphocytes.As a matter of fact,signs of inflammation of atherosclerotic plaques have been observed for centuries and also constituted the basis for a fierce controversy in the19th century between the prominent Austrian pathologist Carl Von Rokitantsky and his German counterpart,Rudolf Virchow.while the former attributed a secondary role to these inflammatory arterial changes,Virchow considered them to be of primary importance.Using modern sophisticated immunohistochemical and immunofluorescence techniques,T lymphocytes and other lymphomonocyte have been found in atherosclerosis plaque.Commonly used experimental mouse models,such as mice rendered hypercholesterolemic by targeted deletion of genes encoding molecules involved in cholesterol metabolism(such as apolipoprotein E Apoe-mice) or the receptor for low-density lipoprotein(LDL;ldlr-/-mice),are very useful for delineating the mechanisms of disease initiation and early growth.Studies of mouse models of atherosclerosis,such as Apoe-/-and ldlr-/-mice,in combination with mice deficient in both B cells and T cells,have demonstrated a substantial role for the adaptive arm of immunity in atherosclerosis.The progeny of Apoe-/-mice crossed with lymphocyte-deficient mice lacking recombination-activating gene1or2or mice with severe combined immunodeficiency have much less atherosclerosis.AS as a chronic inflammatory disease get more and more confirmed.High consistency cholesterol in blood is confirmed as the princeps factor to initiative the process of AS.Cholesterol is transported in the blood by LDL.These particles contain esterified cholesterol and triglycerides surrounded by a shell of phospholipids, free cholesterol and apolipoprotein B100(ApoB100). Circulating LDL particles can accumulate in the intima, the innermost layer of the artery. Here ApoB100binds to proteoglycans of the extracellular matrix through ionic interactions. This is an important initiating factor in early atherogenesis.As a consequence of this subendothe-lial retention, LDL particles are trapped in the intima, where they are prone to oxidative modifications caused by enzymatic attack of myeloperoxidase and lipoxygenases, or by reactive oxygen species such as HOCl, phenoxyl radical intermediates or peroxynitrite gen-erated in the intima during inflammation and atherosclerosis. The peroxidation of fatty acid residues in phospholipids, cholesteryl esters and triglycerides generates reactive aldehydes and truncated lipids. Among the latter, modified phospholipids such as lysophosphatidyl-choline and oxidized1-palmitoyl-2-arachidonyl-sn-glycero-3-phos-phocholine can initiate innate inflammatory responses.DCs with oxLDL inject Apoe-/-mice can startup AS.Activated T lymphocyte can promote macrophage and smooth muscle cell to phagocytose lipid,produce more foam cells and accelerate the process of AS.The quantitative and functional of peripheral blood dendritic cells have pronounced change, the amount of CD11c+mDC decreased obviously but CD11c-pDC have no changed. mDC/pDC≥4have important meaning to differentiate the stable angina and unstable angina. Circulating numbers of CD11c+mDCs and CD123+pDCs and frequencies of CD86+and CCR-7+(CC chemokine receptor type7) mDCs, but not pDCs, were declined in CAD. In addition, plasma Flt3L, but not GM-CSF, was lower in patients and positively correlated with blood DC counts. In response to LPS, mDCs up-regulated CD83and CD86, but CCR-7expression and IL-12secretion remained unchanged, similarly in patients and controls. Conversely, pDCs from patients had lower CD83and CCR-7expression after overnight incubation and had a weaker IQ-induced up-regulation of CD83and IFN-alpha secretion. In conclusion, the results suggest that reduced blood DC counts in CAD are, at least partly, due to impaired DC differentiation from bone marrow progenitors. Decreased levels of mDCs are presumably also explained by activation and subsequent migration to atherosclerotic plaques or lymph nodes. Although mDCs are functioning normally, pDCs from patients appeared to be both numerically and functionally impaired.DCs also play an important role in the process of cranial vascular AS. Dendritic cells have found in carotid artery atherosclerosis plaques, and the risk of plaque fracture was10times significantly higher in complicated than in uncomplicated plaques.The number of DCs have significant related with stroke caused by carotid artery atherosclerosis. Cerebralvascular especially the vessel in the intracalvarium have particular anatomic structure compare with other arteries which have underdevelopment smooth muscle layer and adventitia.Not much experiment have been done to explan the relationship between DCs and cerebralvascular atherosclerosis,more evidences need to be got to expound the role of DCs in the pathological process of cerebralvascular atherosclerosis.If inflammation in faith play an important role in process of AS,then as the most important antigen-presenting cells,the quantity and function of DCs in periphey blood patients with AS should take place some change.As the same to say,the quantity and function of DCs in periphey blood patients with cerebrovascular stenosis caused by AS will arise some change,and this change will vary with the grade of the cerebrovascular stenosis.Its will help us to test and verify the function of inflammation in AS from sidewise approach,and validate each other with the change of DCs in periphey blood patients with coronary heart disease.To study the proportioned changes of peripheral blood dendritic cells(DCs) in patients with different degrees of cerebrovascular stenosis and after stand implanted and explore the relation between DCs and cerebrovascular stenosis.We choose the patients who are in hospital in department of neurology zhujiang hospital between11th,2009to12th,2010as the subject investigated.The reason of cerebrovascular stenosis regard as AS pass through strict filtration.The observation vessel include:common carotid artery,internal carotid artery,vertebral artery,basilar artery,M1section of middle cerebral artery,P1section of posterior cerebral artery,A1section of anterior cerebral artery.Measure the degree of cerebrovascular stenosis according to the NASCET method.To be grouped according to the most serious vessel when there have multiple sites cerebrovascular stenosis.Sixtythree patients were divided into control(no cerebrovascular stenosis),mild stenosis(cerebrovascular stenosis<70%),severe stenosis(cerebrovascular stenosis≥70%) and stand implanted(after stand posting) groups according the result of digital subtraction angiography(DSA) and the situation of clinical. Takeing4ml arterial blood immit EDTA cuvette(heparin1mg:5ml anticoagulation) and record the situation of sex,age,blood pressure,smoking, drinking,diabetes mellitus,cholesterin and so on.Detecting the subset of DCs in periphery blood by flow cytometry.The percentage of peripheral blood myeloid dendritic cells(mDCs) was different comparsion among groups(P<0.0001) whereas no obvious difference was founded in plasmacytoid dendritic cells(pDCs) among them(P=0.065).In comparison with patients with negative result in cerebrovascular according DSA,those with mild stenosis cerebrovascular had no significantly different percentages of mDCs(P=0.275) the same as those with stand implanted group (P=0.473),while the severe stenosis group showed obvious difference between them(P=0.040).The percentage of mDCs was significantly decreased in severe stenosis group than in mild stenosis group(p=0.000),and no significant difference was found between severe stenosis group and stand implanted group(P=0.297),without no obvious difference(P=1.000) between the mild and stand implanted groups was found too.The percentage of mDCs suggest the alterations of the different degrees of cerebrovascular stenosis in patients. |
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