1.A study of the dynamic evolution of macrophage infiltration behavior after acute carotid artery thrombosis
Shikai LI ; Jia LIANG ; Yanyan HE ; Qianhao DING ; Chenqing LI ; Yang LIU ; Yingpu FENG ; Wenli ZHAO ; Yumeng HUANG ; Lina SUO ; Tianxiao LI ; Yingkun HE
Chinese Journal of Cerebrovascular Diseases 2024;21(7):433-443
Objective To explore the changes in macrophage infiltration behavior during the dynamic evolution of thrombi following the formation of acute carotid artery thrombosis occlusion(ACTO).Methods 15 healthy male New Zealand rabbits were selected to establish an ACTO model by causing injury to the rabbit carotid artery using surgical sutures treated with ferric chloride.All rabbits were randomly divided into 5 groups according to the end-point time using the random number table method,namely 24-hour group,1 week group,4week group,8 week group,and 12week group postoperatively,with 3 rabbits in each group.At 24 hours post-operation,the ACTO model was examined by DS A.At 24 hours,1 week,4 weeks,8 weeks,and 12 weeks post-operation,samples were taken from the thrombotic arterial segment of the 3 rabbits in each group and embedded in paraffin.The thrombus samples were stained with hematoxylin-eosin(HE)and Martius scarlet blue(MSB)to analyze changes in thrombus morphology and composition(including red blood cells,fibrin and collagen fibers).Orbit Imaging Analysis software was used for semi-quantitative analysis of the thrombus composition components.Using immunohistochemistry to detect the distribution of MO and M2 macrophages in thrombi,aimed to summarize the dynamic evolution of thrombus morphology,composition,and macrophage infiltration behavior at different stages following ACTO occurrence.Results The 24-hour DSA results indicated that all experimental rabbits successfully established the ACTO model.(1)HE staining showed a continuous increase in thrombus size from 24 hours to 1 week.By 4 weeks,signs of thrombus dissolution appeared,and at 8 weeks,neovascularization was observed within the thrombus.By 12 weeks,signs of fibrosis were evident in the thrombus.(2)MSB staining revealed that during the acute phase of thrombus formation(within 24 hours after surgery),red blood cells were the predominant component initially,but after this period,fibrin and collagen fibers became the main components.(3)The detection results of MO macrophages showed that 24 hours after surgery,MO macrophages in the thrombus were not evenly distributed throughout the thrombus,but mainly gathered at the thrombus edge;at 1 week after surgery,the positive area percentage of MO macrophage in the thrombus increased compared with 24 hours after surgery(thrombus edge:[41.7±27.0]%vs.[24.6±16.7]%,thrombus core:[35.7±19.6]%vs.[11.1±10.4]%,all P<0.001),and evenly distributed within the thrombus;at 4 weeks after surgery,MO macrophages in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.7±6.1]%vs.[41.7±27.0]%,thrombus core:[12.1±8.5]%vs.[35.7±19.6]%,all P<0.001),the differences were statistically significant.At 4,8,and 12 weeks after surgery,MO macrophages within the thrombus did not change significantly with time(thrombus edge:[10.7±6.1]%,[8.0±7.7]%,and[8.9±5.3]%;thrombus core:[12.1±8.5]%,[9.5±4.2]%,and[15.7±11.0]%),and the differences were not statistically significant(all P>0.05).In addition,at 12 weeks after surgery,MO macrophages at the thrombus edge was less than the thrombus core([8.9+5.3]%vs.[15.7±11.0]%,P<0.01).The detection results of M2 macrophages showed that 24 hours after surgery,M2 macrophages in the thrombus were widely distributed throughout the thrombus;at 1 week after surgery,the positive area percentage of M2 macrophages in the thrombus increased compared with 24 hours after surgery(thrombus edge:[22.1±11.3]%vs.[11.4±8.7]%,P<0.001;thrombus core:[24.5±9.8]%vs.[7.6±6.0]%,P<0.001);at 4 weeks after surgery,M2 macrophage in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.6±3.7]%vs.[22.1±11.3]%,P<0.001;thrombus core:[9.2±4.3]%vs.[24.5±9.8]%,P<0.001);at 8 weeks after surgery,M2 macrophages in the thrombus increased compared with 4 weeks after surgery([17.9±8.8]%vs.[9.2±4.3]%,P<0.001),and the differences were statistically significant.However,M2 macrophages in the thrombus did not change significantly from 8 weeks to 12 weeks after surgery(thrombus edge:[9.4±6.3]%vs.[8.5±5.3]%,P>0.05;thrombus core:[17.9±8.8]%vs.[14.4±10.0]%,P>0.05).In addition,at 8 and 12 weeks after surgery,M2 macrophages in the thrombus core was greater than the thrombus edge(8 weeks after surgery:[17.9±8.8]%vs.[9.4±6.3]%,P<0.001;12weeks after surgery:[14.4±10.0]%vs.[8.5±5.3]%,P<0.001).Conclusions This study successfully established an ACTO animal model and demonstrated for the first time the dynamic evolution of macrophages within 12 weeks post-thrombus formation.Macrophages may played a significant role in both thrombus formation and fibrinolysis,as well as in the promotion of thrombus dissolution and the formation of new blood vessels within the thrombus which may potentially promote the spontaneous reperfusion of the occluded vessels.The results of this study need further verification.
2.Analysis of related factors for vascular luminal dilatational remodeling after balloon angioplasty for intracranial atherosclerotic stenosis
Qianhao DING ; Yingkun HE ; Jingge ZHAO ; Yanyan HE ; Wenbo LIU ; Yao TANG ; Dehua GUO ; Tengfei ZHOU ; Liangfu ZHU ; Ziliang WANG ; Tianxiao LI
Chinese Journal of Radiology 2024;58(8):850-858
Objective:To explore the factors associated with vascular luminal dilatational remodeling (VLDR) following balloon angioplasty for intracranial atherosclerotic stenosis (ICAS).Methods:A case-control study was conducted to analyze the data of symptomatic severe ICAS patients who received either paclitaxel-coated balloon angioplasty (PCBA) or plain balloon angioplasty (POBA) at our center from January 2019 to January 2022 and completed the six-month follow-up. The patients were divided into VLDR group and non-VLDR group according to whether VLDR occurred on follow-up digital subtraction angiography (DSA). The baseline data, preoperative and postoperative lesion characteristics (DSA), and perioperative related information were collected. The definition of VLDR was a decrease in luminal stenosis rate by more than 10% at the time of follow-up compared to the immediate postoperative period. Multivariate logistic regression was performed to analyze possible factors affecting VLDR such as balloon type, balloon length, and expansion time.Results:A total of 88 patients were included in this study, with 16 in the VLDR group and 72 in the non-VLDR group. The follow-up time for all included patients was 6.00 (5.00, 7.00) months. VLDR occurred in 18.2% (16/88) of cases, with a VLDR incidence of 30.4% (14/46) after PCBA and 4.8% (2/42) after POBA. Univariate logistic regression analysis revealed that treatment balloon type, balloon length, inflated time, immediate postoperative stenosis rate, follow-up time and Mori classification may affect the occurrence of VLDR. Multivariate logistic regression analysis showed that the use of paclitaxel-coated balloon (PCB) ( OR=9.82, 95% CI 1.99-48.49, P=0.005) and postoperative immediate stenosis rate ( OR=1.07, 95% CI 1.00-1.14, P=0.042) were independently associated with VLDR. Conclusion:The occurrence of VLDR following balloon angioplasty in ICAS was associated with the use of PCB and immediate postoperative stenosis rates, which will provide guidance for the clinical application of PCB.