Objective To investigate the change of vasa vasorum in vessel wall of varicose vein of the lower extre-mity. Methods Thirty-two patients with varicose vein of the lower extremity were collected， in which of 12 patients with simple varicose veins （varicose group）， 9 patients with recurrent varicose veins （recurrent group）， 11 patients withthrombophlebitis of varicose vein （thrombophlebitis group）， 9 patients with normal venous tissue as control group. HE staining was performed to observe the distribution of vasa vasorum and detect the vasa vasorum density. Results The increasing vasa vasorums were observed in the adventitia and media， but few was observed in the intima in the varicose， recurrent， and thrombophlebitis groups. The distribution of vasa vasorum was in the adventitia in the control group. The vasa vasorum densities （/mm2） in the varicose， recurrent， and thrombophlebitis groups （5.65±1.45，6.20±1.73， and 5.94±1.63， respectively） were greater than those in the control group （2.87±0.54）， the difference wasstatistically significant （P＜0.05）， but there was no significant difference of the vasa vasorum density among the varicosevein， recurrent， and thrombophlebitis groups （P＞0.05）. Conclusion Change of vasa vasorum is an important pathol-gical change with the nosogenis of varicose vein of the lower extremity.
Objective To investigate the dynamic changes of vascular adventitia and collagen distribution in the vein graft restenosis model, and evaluate the effects of adventitia and collagen distribution on intimal hyperplasia and vascular remodeling. Methods The pig autogenous vein grafts restenosis model from 18 longwhite pigs were created. 18 pigs were divided into 3 groups: 7th day group after operation, 30th day group after operation and 45th day group after operation according to animals harvested after surgery. The preoperative graft was as control group. According to HE and Masson staining slices, the vascular thickness, cell density, collagen distribution and vascular remodeling were investigated by histomorphometrical approach. Results In 7th day group after operation, the neointima formed and continuously thickened. The thickness and cell density of adventitia increased gradually, and the collagen of adventitia and neointima gradually increased, the luminal area gradually decreased after operation, but have no significant difference with control group（F=2.03,P=0.091）. The residual restenosis rate increased inversely（F=5.16,P=0.033）. Remodeling index and external elastic lamina area (EELA) slightly increased. In 30th day group after operation, the neointima thickened significantly, the thickness and cell density of adventitia reached the peak. There were a significant increase in the collagen of neointima, and the collagen of adventitia reached maximum. The luminal area and inter elastic lamina area(IELA) reduced distinctly as compared with 7th day group, the residual restenosis rate increased significantly（F=6.63,P=0.018）, but remodeling index and EELA decreased distinctly as compared with 7th day group after operation. In 45th day group after operation, the thicknessof neointima reached maximum, but the cell density of adventitia reduced distinctly compared with 30th day group after operation（F=6.91, P=0.015）. The collagen of neointima reached maximum, but the collagen of adventitia were smaller than those in 30th day group after operation, and there were some local fibrosis in adventitia. The luminal area, remodeling index, IELA and EELA reached minimum, but the residuum restenosis rate reached maximum. Conclusion Vein grafts restenosis is resulted by intimal hyperplasia and vascular remodeling. The thickness and fibrosis of adventitia and rearrangement of collagen are the important factors on intimal hyperplasia and vascular remodeling, which takes part in and accelerate the course of vein restenosis.
Objective To study the intervention effect of ginkgo biloba extract（GBE） on airway and vascular remodeling in rat model of chronic obstructive pulmonary disease(COPD).Methods Forty wistar rats were randomly divided into group A，B，C and D.The rat model of COPD were established by intratracheally injection of lipopolysaccharide and exposure to cigarette smoke in groups B，C and D.Groups C and D were given intraperitoneally injection with 40 mg/kg GBE respectively from day1 to day14 and day29 to day42.Forty-three days later，the rats were sacrificed for lung pathological examination.Results Group B，C and D all showed pathological changes characteristic of COPD to different extent.The average area and standard number of alveoli showed significant difference between each groups（all Plt;0.01）.The structure of bronchiole walls in group C and D show mild changes.The ratio of bronchial smooth muscle thickness to bronchial wall thickness and bronchial wall area to bronchial area of group C and D showed significant difference when compared with group A and B（all Plt;0.01）.The vascular smooth muscle cell of group C and D had mild hyperplasia and the vascular wall had slightly thickened.The ratio of vascular smooth muscle thickness to vascular wall thickness and vascular wall area to vascular area in group C and D showed significant difference when compared with group A and B（all Plt;0.01）.Conclusion GBE has inhibitory effects on airway and vascular remodeling in rats model of COPD.
ObjectiveTo investigate the effect of ADAM33 gene silencing in VSMCs on the proliferation and lumen formation of airway vascular endothelial cells (VECs) in a co-culture system and the possible regulatory mechanism. MethodsThe Human aortic smooth muscle cells (HASMCs) and human pulmonary microvascular endothelial cells (HPMECs) were used to construct a cell co-culture system. ADAM33 gene expression was silenced by lentivirus transfection technique, and the subjects were divided into endothelial cell blank group, co-culture group, co-culture +shRNA negative control group, and co-culture + ADAM33-SHRNA group. The expressions of sADAM33, VEGFA,VEGER2, ang-1 and ang-2 in co-culture system were detected by ELISA. The proliferation and lumen formation of HPMECs were observed by CCK-8 and Transwell experiments. The protein expression of Tie2, PI3K, Akt, and mTOR key molecules in Tie2/PI3K/Akt/mTOR signaling pathway and the phosphorylation levels of AKT and mTOR were detected by Western-blotting method. Results① Compared with the co-culture group (0.851±0.036) and the co-culture + shRNA negative control group (0.828±0.047), the OD value of the co-culture + ADAM33shRNA group (0.699±0.038) was significantly decreased (P<0.05). ② Compared with the co-culture group (159.169±15.740) and the co-culture +shRNA negative control group (157.357±21.612), the tube length of the co-culture +ADAM33shRNA group (120.812±2.791) was also significantly decreased (P<0.05). ③ After ADAM33 gene expression of HASMCs was silted in co-culture system, the expression levels of VEGFA, VEGFR2, ang-1 and ang-2 were significantly decreased (P<0.05), while the expression levels of Tie2, PI3K, P-Akt and P-mtor were decreased (P<0.05). ConclusionsSilencing the expression of the ADAM33 gene could reduce the release of sADAM33 from the membrane of the airway VSMCs, regulate the proliferation and lumen formation of airway VECs by reducing the expression of VEGF/VEGFR and inhibiting the activities of the Tie2/PI3K/Akt/mTOR signaling pathways,and then participate in airway vascular remodeling in asthma.
ObjectiveTo investigate the expression of extracellular signalregulated kinase (ERK) and p38 mitogenactivated protein kinase （p38 MAPK） in autogenous vein grafts during vascular remodeling.MethodsAn autogenous vein graft model was established by transplanting the right jugular vein to infrarenal abdominal aorta in 80 Wistar rats. Vein graft samples were harvested 6 hours, 24 hours, 3 days, 7 days, 2 weeks, 4 weeks, 6 weeks and 8 weeks after surgery. Gene expression of ERK and p38 MAPK was measured by reverse transcriptionPCR. Western blot was used to detect the expression of protein products and phosphorylation protein products of ERK and p38 MAPK. Apoptosis of vascular smooth muscle cells (VSMCs) was determined by TUNEL. Proliferating cell nuclear antigen(PCNA) of VSMCs also was studied.ResultsThe expression of ERK1 mRNA and p38 MAPK mRNA increased considerably after surgery. ERK1 mRNA reached the peak on the 7th day 〔（33.2±14.2）%, P＜0.01〕, but p38 MAPK mRNA reached the peak on the second week after surgery 〔(58.8±26.2）%, P＜0.01〕. The expression of ERK1/2 detected by western blot reached the peak during 1 to 2 weeks and decreased gradually to normal level 6 weeks after surgery. The expression of p38 MAPK reached the peak during 2 to 4 weeks and decreased to 1/4 to 1/2fold 8 weeks after surgery. There was a positive relationship between ERK1 and PCNA(r=0.759 6，P＜0.01) and a positive relationship between p38 MAPK and apoptosis(r=0.892 2，P＜0.01). ConclusionActivation of MAPK system exists in autogenous vein grafts and it may become a new target for the therapy of stenosis after vein grafts.
Aortic aneurysm and dissection are critical cardiovascular diseases that threaten human life and health seriously. No pharmacological treatment can effectively prevent disease progression. The imbalance of aortic wall cells and non-cellular components leads to structural or functional degeneration of the aorta, which is a prerequisite for disease occurrence. As the important non-cellular component, extracellular matrix (ECM) is crucial to maintain the aortic structure, function, and homeostasis. Abnormal production of elastin and collagen, destruction of cross-linking between elastic fibers and collagen fibers, and the imbalance of metalloproteinase and inhibitors leads to excessive degradation of ECM proteins, all of which have destroyed the structure and function of aorta. It will provide more ideas for disease prevention and treatment by learning ECM proteins and their metabolic mechanism. Here, we focus on the ECM proteins that have been reported to be involved in aortic aneurysm and dissection, and discuss the regulatory mechanism of metalloproteinase and inhibitors.
As essential immune cells for retinal homeostasis and repair, macrophages play a pivotal role throughout vascular remodeling, a central pathological feature of diabetic retinopathy (DR). Emerging evidence indicates that macrophages actively adapt to the diabetic microenvironment through metabolic reprogramming. Notably, lipid metabolic reprogramming plays a crucial role in shaping macrophage activation phenotypes, modulating immune functions, and regulating the synthesis of inflammatory mediators, thereby influencing vascular remodeling. A deeper understanding of lipid metabolic reprogramming in macrophage-mediated vascular remodeling may provide novel immunometabolic targets for therapeutic intervention in DR.
