Study On The Pathology, Morphology And Related Cellular Mechanisms Of Carotid Atherosclerotic Plaque

BackgroundThe unstable plaques in atherosclerotic plaques are closely related to the occurrence of clinical symptoms.At present,the thickness of fibrous cap and the size of lipid core are important reference factors to distinguish the stability of atherosclerotic plaques.With the deepening of imaging and pathological studies,more and more attention has been paid to Angiogenesis and vascular smooth muscle cells in atherosclerotic plaques.Whether the distribution,density and morphology of the two plaques are closely related to the occurrence of clinical symptoms deserves further investigation and study.Endothelial progenitor cells(EPCs)are important precursor cells.The number and function of EPCs are related to cardiovascular and cerebrovascular diseases.It is important to explore the interaction of EPCs in angiogenesis and vascular smooth muscle.AimTo observe the role of neovascularization and vascular smooth muscle cells(VSMCs)in carotid atherosclerosis plaque in different clinical symptoms,to simulate the occurrence of angiogenesis and vascular smooth muscle cells(VSMCs)in vitro by using endothelial progenitor cells(EPCs),and to explore their roles and mechanisms in the occurrence and development of clinical symptoms.MethodsCarotid endarterectomy specimens were collected from 52 patients with carotid atherosclerotic stenosis.According to the clinical symptoms,the patients were divided into two groups:asymptomatic group and symptomatic group.Asymptomatic group:carotid artery stenosis without focal ischemic symptoms;Symptomatic group:transient ischemic symptoms,such as TIA or ipsilateral haze,occurred 4 weeks before operation.All patients underwent Color Doppler ultrasonography(CDU)or computed tomography angiography(CTA)before operation.The number,morphology and distribution of neovascularization and vascular smooth muscle cells in patch specimens collected from patients were summarized by pathological section analysis.The correlation between neovascularization and clinical symptoms was studied.The characteristics of neovascularization in different pathological types and stages were discussed.Endothelial progenitor cells were used to induce differentiation into mature vascular endothelial cells and vascular smooth muscle cells in vitro.Cells,clarify the specific cellular mechanism of angiogenesis.ResultsThe average cross-sectional area of neovascularization in the asymptomatic group was smaller than that in the symptomatic group(P<0.05),and the density of neovascularization was lower than that in the symptomatic group(P<0.001).The distribution of neovascularization in the plaque was higher in the symptomatic group than in the asymptomatic group(P<0.001).In the symptomatic group,irregular branching vessels were dominant,mainly distributed in shoulder and fibrous cap,while in the asymptomatic group,circular regular vessels were dominant,mainly distributed in the base of plaque.In general morphology,the proportion of common plaque in asymptomatic group was higher than that in symptomatic group(P<0.001),the proportion of ruptured plaque in symptomatic group was higher than that in asymptomatic group(P<0.01),and the proportion of hemorrhagic plaque in symptomatic group was also higher than that in asymptomatic group(P<0.05).In microscopical morphology,the proportion of stage 4 plaques in the asymptomatic group was higher than that in the symptomatic group(P<0.05),while the proportion of stage 6 plaques in the symptomatic group was higher than that in the asymptomatic group(P<0.001),but there was no significant difference between the two groups(P=0.05).The density of venous neovascularization in asymptomatic group was lower than that in symptomatic group(P<0.001),but there was no difference between the two groups(,P>0.05).In the symptomatic group,there were differences in the common plaque,hemorrhagic plaque and ruptured plaque among different types of neovascularization(P=0.04,P=0.01,P=0.02).At the same time,there were also differences in the arteriovenous density of neovascularization among the four,five and six stages of plaque(P=0.04,P=0.02,P<0.001).In general pathology,there were no differences in the neovascularization among the four,five and six stages of plaque(P>0.05).In hemorrhagic plaques,the density of venous neovascularization was higher than that of arterial neovascularization(P=0.02,P=0.03,P<0.001).In ruptured plaques,the density of venous neovascularization was higher than that of arterial neovascularization in stage 5 and 6 plaques(P=0.04,P<0.001).VSMCs in the asymptomatic group were higher than those in the symptomatic group(P<0.05);VSMCs in the stable plaque were higher than those in the unstable plaque(P<0.05);VSMCs in the basal,shoulder and fibrous cap were higher than those in the symptomatic group(P<0.05);with the increase of the thickness of fibrous cap,the number of VSMCs increased,showing a positive correlation.CD 133-labeled EPCs were distributed in human carotid atherosclerotic plaques,mainly around neovascularization.The types of neovascularization could be identified by specific markers of arteriovenous endothelium.EPCs derived from human embryos could be induced to differentiate into mature arteriovenous endothelial cells and vascular smooth muscle cells in vitro,and had the function of endothelial cells.conclusionThe distribution of neovascularization and smooth muscle in carotid atherosclerotic plaque is related to the occurrence of clinical symptoms.Venous neovascularization plays an important role in the occurrence of clinical symptoms.Vascular smooth muscle stabilizes the plaque by secreting extracellular matrix and is positively correlated with the thickness of fibrous cap.EPCs derived from human embryonic aorta can be induced to differentiate into mature and functional vascular endothelial cells and vascular smooth muscle cells in vitro.BackgroundFor a long time,traditional cardiovascular risk factors cannot fully explain the occurrence and development of atherosclerosis.A large number of clinical studies have observed that carotid atherosclerotic plaques mainly occur in the bifurcation of the carotid artery,so the shape of the carotid artery plays an important role in it by affecting the hemodynamics;the stability of the plaque is related to the "quantity and quality" of extracellular matrix,and the size of different angles produces different hemodynamics,thus affecting the "quantity and quality" of extracellular matrix.AimTo explore the role of carotid artery morphology in carotid atherosclerosis and its effect on extracellular matrix.Methods193 patients were selected and divided into asymptomatic group and symptomatic group according to their clinical symptoms.Carotid artery blood flow velocity(cm/s)and carotid artery diameter(mm)were measured by carotid ultrasound,blood viscosity(mPa.s)was measured by blood sampling,and blood shear force(dynes/cm2)was calculated.According to the results of carotid CTA,the size of carotid bifurcation angle(0),the size of internal carotid angle(°)and the height of carotid bifurcation angle were measured respectively.At the same time,the content of extracellular matrix in carotid atherosclerotic plaque was quantitatively determined,mainly the content of collagen and proteoglycan.Results111 asymptomatic patients and 82 symptomatic patients were included in the study.The average carotid bifurcation angle in the asymptomatic group was 60.9 ± 1.6,67.1±2.1,the average internal carotid artery angle in the asymptomatic group was 153.8±1.5,and in the symptomatic group was 141.3 ± 1.5,the average carotid artery blood flow shear stress was 17.6 ±0.1(dynes/cm2)in the asymptomatic group and 16.7±0.1(dynes/cm2)in the symptomatic group.Carotid bifurcation angle were higher in symptomatic group than in asymptomatic group,while internal carotid angle and carotid artery blood flow shear stress was lower in symptomatic group than in asymptomatic group(P<0.05).The normal carotid bifurcation angle was mainly located in the upper 1/3 of the fourth cervical vertebra,the high carotid bifurcation angle was mainly located in the upper 1/3 and the middle 1/3 of the third cervical vertebra,and the lower carotid bifurcation angle was mainly located in the middle 1/3 of the fifth cervical vertebra.The size of the carotid bifurcation angle increases with the increase of the height of the carotid bifurcation angle,while the internal carotid angle and blood shear stress decrease with the increase of the height.The carotid bifurcation angle,internal carotid artery angle and blood flow shear stress increased or decreased by 4.8 degrees,6.9 degrees and 0.6(dynes/cm2)with each increase or decrease of one third of the intervertebral disc or vertebral body;the average height of carotid bifurcation angle was 5.8 in asymptomatic group and 5.4 in symptomatic group(P>0.05);the average height of carotid bifurcation angle was 1/3 above the fourth cervical vertebra in asymptomatic group,and the average height of carotid bifurcation angle was 5.8 in asymptomatic group in the symptomatic group,the intervertebral disc was located in the third and fourth intervertebral discs on average.Carotid bifurcation angle was negatively correlated with blood flow shear stress,internal carotid artery angle and blood flow shear stress were negatively correlated,and internal carotid artery angle was positively correlated with shear stress.The average thickness of fibrous cap in asymptomatic group and symptomatic group was 482.7 17.7mm and ±432.6 16.6mm,respectively,higher than that in symptomatic group(P<0.05).Similarly,the average thickness of the thinnest part of fibrous cap in asymptomatic group and symptomatic group was 302.7 ± 12.3 mm and 257.60± 12.6 mm,respectively,higher than that in asymptomatic group(P<0.05).The contents of collagen in asymptomatic group and symptomatic group were 55.1±2.4 and 48.4± 1.9,respectively(P<0.05),while the contents of proteoglycan in asymptomatic group and symptomatic group were 16.3±0.6 and 24.6± 1.1,respectively(P<0.001).Collagen was mainly distributed in fibrous cap in asymptomatic group,while proteoglycan was more distributed in thin fibrous cap in symptomatic group,near calcified area and necrosis lipid core area.Carotid bifurcation angle was negatively correlated with the thickness of fibrous cap,positively correlated with collagen and negatively correlated with proteoglycan,positively correlated with the thickness of fibrous cap,negatively correlated with collagen and positively correlated with proteoglycan.The contents of YAP in the asymptomatic group and the symptomatic group were 3153.0± 178.7 and 3647.2±229.5,respectively.The contents of YAP in the symptomatic group were lower than those in the asymptomatic group(P<0.001).YAP was mainly distributed near the calcified area and neovascularization;the distribution of YAP was negatively correlated with carotid bifurcation angle,but positively correlated with internal carotid artery angle and blood flow shear force.ConclusionThe occurrence of clinical symptoms is related to the shape and height of carotid artery.The bigger angle and higher position of carotid bifurcation angle can produce larger blood flow shear force,which can affect the increase of proteoglycan and YAP expression,thus promoting the occurrence of atherosclerosis.