Patterns of internal elastic lamina morphology in the canine common carotid artery

The internal elastic lamina (IEL) of normal canine carotid arteries was examined by scanning electron microscopy in pressure-fixed specimens with intact endothelium. IEL appearance showed a marked variation between animals and was classified into fenestrated sheet, fibrous, and mixed varieties. This interpretation of the apparent morphology was confirmed with transmission electron microscopy. It was clear that IEL fenestrae were associated with surface depressions and that in areas of fibrous IEL there was surface elevation over individual fibres. Within individual animals there was little variation in the pattern of IEL either along or between common carotid arteries. If theories of atherogenesis involving the IEL are correct, the variation of IEL patterns between animals would suggest a corresponding variation of incidence and severity of atheromatous lesions of the common carotid artery between animals. Further, the occurrence of fibrous areas distributed throughout the fenestrated sheet would suggest a focal distribution of lesions along such arteries.     

Echocardiographic and Doppler evaluation of the aortic arch and brachiocephalic vessels in cerebral and systemic arteriovenous fistulas

Congenital arteriovenous fistulas presenting in the newborn period pose difficult diagnostic problems and simulate structural heart disease. Angiocardiography, when performed, demonstrates enlarged brachiocephalic vessels and rapid cerebral venous return. The value of echocardiographic imaging and measurement of the aortic arch and brachiocephalic vessels, and evaluation of the Doppler flow profile in these vessels as a means of making a rapid diagnosis of cerebral or thoracic arteriovenous fistula, was therefore assessed in 10 infants with these diagnoses seen over a 4 year period (1983 to 1987). Twenty-nine infants (median age 6 weeks) undergoing two-dimensional echocardiography but with no significant lesions were prospectively selected as controls. Nine of the 10 patients had congestive heart failure at presentation (mean age 2 days). A cranial bruit was heard in three and arteriovenous fistula was suspected in five patients. Aortic arch segments and brachiocephalic vessel dimensions expressed as ratios of the abdominal aorta showed significantly larger values in patients for the ascending aorta (p = 0.01), innominate artery (p less than 0.001), right and left subclavian arteries (p less than 0.001) and left common carotid artery (p less than 0.05). The thoracic descending aorta was, however, significantly smaller in patients (p less than 0.002). Retrograde diastolic Doppler flow in the descending aorta proximal to the ductus arteriosus and anterograde diastolic flow with a mean spectral flow-time integral 27% of systolic were present in patients only, whereas Doppler diastolic flow in brachiocephalic vessels, present in 5 of 29 control infants, was less than 15% of systolic flow and not accompanied by dilation of these vessels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related changes in aortic intima of rats.

The aortic intima of young and old Wistar rats was studied by light and electron microscopy. The endothelial cells of young rats are flat and regular and lie adjacent to the internal elastic lamina (IEL). Endothelial cells of old rats have irregular shapes and sizes and bulge into the lumen. Long protrusions connect these cells to the IEL through a layer of granular and fibrillar material that separates the IEL from the endothelium. This material is PAS and Alcian blue positive and increases with age. There are twice as many pinocytic vesicles on the luminal front of endothelial cells of old rats as compared to the tissue front. Endothelial cells of young rats have similar numbers of vesicles on the two fronts. No significant difference was found between the charge density of the luninal plasmalemma of young and old rats; however, significantly less sialyl groups were found on endothelial cells of old rats. A marked difference in the labeling pattern of the IEL by cationized ferritin (CF) was observed between young and old rats.     

硬脑膜动静脉瘘动物模型的建立

目的观察吻合右侧颈动静脉并闭塞左侧横窦和上矢状窦前部造成颅内静脉窦高压模型后，能否产生硬脑膜动静脉瘘。方法将51只体重为200～250g的SD雄性大鼠随机分成两组：(1)实验组：45只大鼠，接受吻合右侧颈总动脉和颈外静脉并闭塞左侧横窦和上矢状窦前1／3的手术。(2)对照组：6只大鼠，仅解剖颈部血管和硬脑膜窦而不吻合或闭塞。术后90d行全脑血管造影，观察有无动静脉瘘。结果实验组有28只大鼠出现面部动静脉瘘，其中6只出现硬脑膜动静脉瘘，出现率为13．3％。对照组大鼠未见动静脉瘘。结论颈动静脉吻合后合并静脉窦闭塞的大鼠静脉窦高压模型能产生类似临床的硬脑膜动静脉瘘，可以作为研究硬脑膜动静脉瘘的动物模型。     

Electron microscopic studies of cat mesenteric arterioles: A structure-function analysis

Arcade arterioles of cat mesentery were fixed in vivo at normal and elevated intravascular pressures and studied by transmission electron microscopy. In general, cells, filaments, and extracellular fibrils on the luminal side of the internal elastic lamina (IEL) were oriented longitudinally while those of the abluminal side were oriented circumferentially. The IEL presented a smooth, cylindrical appearance while the intima, media, and adventitia were quite irregular in cross section and longitudinal section. The vessel lumen contour was also irregular, especially in the vicinity of endothelial cell nuclei. Endothelial cell processes (ridges) projected through longitudinal slits (fenestrae) in the IEL and made contact with vascular smooth muscle (VSM) cells, often causing apparent deformation of the latter. VSM cells typically possessed multiple processes which were oriented circumferentially. Within the VSM cells myofibrils were oriented tangential to the vessel circumference. Dense bodies were preferentially located on the adventitial surface of the VSM but were also found at junctions between myocytes, suggesting a means of force transmission between cells. Vessels which were constricted with venous pressure elevation showed substantial changes in conformation of the wall structures, which may reflect considerable mobility of wall elements. Several areas of the VSM cell membrane appear to be deformed with intravascular pressure elevation, which may be important in the myogenic response to the pressure rise.     

Endothelial gaps as sites for plasma leakage in inflammation

Objective : In 1961, Majno and Palade proposed that plasma leakage in acute inflammation caused by histamine, serotonin, or bradykinin results via gaps that form between endothelial cells of postcapillary venules. Now the relevance of endothelial gaps in plasma leakage is being questioned. The purpose of this review is to summarize experimental evidence from our studies showing that endothelial gaps participate in plasma leakage in inflammation. Methods : Using neurogenic inflammation as a model of plasma leakage in acute inflammation, we compared five methods to determine whether endothelial gaps form in the microvasculature of the rat trachea. 1) Endothelial cell borders and gaps were stained with silver nitrate and visualized by light, scanning, and transmission electron microscopy. 2) The luminal surface of endothelial cells was examined by scanning electron microscopy. 3) The luminal surface of endothelial cells was stained with a biotinylated lectin and avidin-biotin-peroxidase histochemistry, and then was examined by differential interference contrast microscopy. 4) Endothelial junctions were reconstructed from serial sections photographed by transmission electron microscopy. 5) Leakage was measured after perfusion of lectins or tracers through aldehyde-fixed vessels in situ. Results : The results from the five methods used in this system were consistent with the formation of gaps between endothelial cells. Endothelial gaps were rare or absent under baseline conditions, but appeared with the onset of plasma leakage and had a distribution that matched the distribution of leakage. Gaps had a complex morphology and were accompanied by fingerlike cell processes, which may anchor adjacent endothelial cells to one another and participate in gap closure. In contrast to normal vessels, vessels that were leaky in life continued to leak after aldehyde fixation, in evidence that, once formed, the leakage pathway did not require energy-dependent membrane movement or vesicle shuttling. Holes through endothelial cells were less than 1% as frequent as intercellular gaps. Conclusions : Taken together, the results show that endothelial gaps are a consistent feature of leaky vessels in the model system we studied, and are not an artifact of a particular method. The morphological complexity of the openings and accompanying fingerlike cell processes and overlapping endothelial cell borders make gaps difficult to distinguish from transcellular holes in thin sections viewed by transmission electron microscopy. However, scanning electron microscopic observations show that most of the openings in leaky venules are intercellular gaps, not transcellular holes. The formation and closure of gaps are likely to be energy-dependent, but the process of plasma leakage is not, provided there is adequate driving force for extravasation. The cellular mechanisms of gap opening and closure remain to be elucidated.     

p47phox-dependent NADPH oxidase regulates flow-induced vascular remodeling

Chronic alterations in blood flow elicit an adaptive response that tends to normalize shear stress, involving nitric oxide (NO) and matrix metalloproteinases (MMPs). To evaluate the role of NADPH oxidase in this process, we developed a new model of mouse arteriovenous fistula (AVF) connecting the right common carotid artery (RCCA) with the jugular vein, which does not affect blood pressure. Mice deficient for gp91phox and p47phox subunits of NADPH and wild-type controls were used. AVF greatly increased RCCA blood flow (0.78+/-0.12 to 4.71+/-0.78 mL/min; P<0.01), producing an abrupt rise in shear stress (35+/-1 to 261+/-17 dynes/cm2; P<0.01) within 24 hours. RCCA diameter (460+/-14 microm) gradually enlarged 1 and 3 weeks after AVF (534+/-14 microm and 627+/-19 microm; P<0.01), reducing shear stress (173+/-13 and 106+/-10 dynes/cm2, respectively). In gp91phox(-/-) mice, changes in RCCA caliber and shear stress matched controls. However, p47phox(-/-) mouse RCCAs enlarged only marginally, such that shear stress remained high (199+/-8 dynes/cm2 at 3 weeks). Likewise, remodeling was minimal in endothelial NO synthase (eNOS)(-/-) mice. In both control and gp91phox(-/-) animals, reactive oxygen species (ROS) production and MMP induction was enhanced by AVF, whereas in p47phox(-/-) and eNOS(-/-) mice such response was negligible. Similarly, nitrotyrosine staining, indicating peroxynitrite formation, was more pronounced in control and gp91phox(-/-) mice than in p47phox(-/-) and eNOS(-/-) mice. Hence, shear stress induces vascular NADPH oxidase comprising p47phox but not gp91phox. Generated ROS interact with NO to produce peroxynitrite, which in turn activates MMPs, facilitating vessel remodeling. Our study provides the first evidence that ROS play a fundamental role in flow-induced vascular enlargement.     

Doppler echocardiographic features of coronary arteriovenous fistula. Complementary roles of cross sectional echocardiography and the Doppler technique

The Doppler echocardiographic features of coronary arteriovenous fistula were investigated in eight patients with left or right coronary arteriovenous fistulas who had a continuous heart murmur in the upper precordial area and whose diagnoses were confirmed by coronary angiography. In four patients the dilated lumen of the coronary arteriovenous fistula was visualised by cross sectional echocardiography. Of these, three showed abnormal unidirectional continuous flow signals with broad velocity spectra in the fistula. Abnormal, powerful, unidirectional or bidirectional continuous Doppler signals were detected in part of the pulmonary artery in two of the eight patients, in part of the right ventricle in two, and in part of the right atrium in one; these signals were interpreted as indicating shunt flow. Although the opening of the fistula was difficult to visualise by cross sectional echocardiography, the pulsed Doppler technique helped identify the site in patients with dilatation of the coronary artery. In the remaining three patients with a small shunt no abnormal findings were obtained with cross sectional echocardiography or the Doppler technique. The size of the fistula below which no abnormal findings may be obtained by Doppler echocardiography still needs to be determined.     

Doppler echocardiographic features of coronary arteriovenous fistula. Complementary roles of cross sectional echocardiography and the Doppler technique.

The Doppler echocardiographic features of coronary arteriovenous fistula were investigated in eight patients with left or right coronary arteriovenous fistulas who had a continuous heart murmur in the upper precordial area and whose diagnoses were confirmed by coronary angiography. In four patients the dilated lumen of the coronary arteriovenous fistula was visualised by cross sectional echocardiography. Of these, three showed abnormal unidirectional continuous flow signals with broad velocity spectra in the fistula. Abnormal, powerful, unidirectional or bidirectional continuous Doppler signals were detected in part of the pulmonary artery in two of the eight patients, in part of the right ventricle in two, and in part of the right atrium in one; these signals were interpreted as indicating shunt flow. Although the opening of the fistula was difficult to visualise by cross sectional echocardiography, the pulsed Doppler technique helped identify the site in patients with dilatation of the coronary artery. In the remaining three patients with a small shunt no abnormal findings were obtained with cross sectional echocardiography or the Doppler technique. The size of the fistula below which no abnormal findings may be obtained by Doppler echocardiography still needs to be determined.     

彩色多普勒血流显像测量同侧肱动脉血流速预测自体动静脉内瘘成熟度的研究

目的 探讨彩色多普勒血流显像(CDFI)测量同侧肱动脉血流速与自体动静脉内瘘（AVF）成熟的相关性。方法 选择2015年12月～2018年8月于我院行头静脉-桡动脉端侧吻合且术后触诊震颤明显的患者141例,收集其临床资料,对AVF前后CDFI检查结果进行比较。结果 141例患者中有116例患者内瘘成熟（成熟组）,25例内瘘成熟不良（成熟不良组）。成熟不良组患者糖尿病患病率和糖尿病肾病为原发病的比例高于成熟组（P＜0.05）;成熟组患者术前头静脉直径大于成熟不良组（P＜0.05）;内瘘成熟组患者术后8周瘘口直径、肱动脉直径、肱动脉最大血流速和肱动脉血流速变化均高于成熟不良组（P＜0.05）。结论 术后早期采用CDFI测定肱动脉直径、肱动脉最大血流速及肱动脉流速变化可预测内瘘是否成熟,用于早期发现内瘘成熟不良。     

Role of matrix metalloproteinases in blood flow-induced arterial enlargement: interaction with NO

Tears in the internal elastic lamina (IEL) can be observed after chronic increases in arterial blood flow, suggesting a potential role for matrix metalloproteinases (MMPs) in flow-induced vascular remodeling. We undertook to study this phenomenon by constructing an arteriovenous fistula (AVF) between the left common carotid artery (CCA) and the external jugular vein in rabbits. The diameter of the flow-loaded left CCA increased by 13.6+/-1.8% by day 3 after construction of the AVF compared with the right CCA (n=4, P:<0.01) and by 40.7+/-7.5% by day-15 (n=10, P:<0.0001). Increased CCA diameter also coincided with IEL fragmentation. Three days after construction of the AVF, gelatin zymography of protein extracts from left CCAs of untreated rabbits showed a significant increase in the 62-kDa (active MMP-2) activity and the appearance of a lytic band at 92 kDa (pro-MMP-9). In further experiments, MMP activity was inhibited by treatment with doxycycline (DOX) or BB-94, a specific MMP inhibitor. The increase in the 62-kDa gelatinolytic band was abolished in DOX- and BB-94-treated rabbits. The 92-kDa gelatinolytic band was also reduced in DOX-treated animals. Furthermore, both increased left CCA diameter and IEL fragmentation were abolished in DOX- and BB-94-treated rabbits. To evaluate whether nitric oxide was involved in blood flow-induced MMP activation, the rabbits were treated with N:(G)-nitro-L-arginine methyl ester to inhibit nitric oxide synthesis. MMP activities were significantly decreased in the left CCAs of N:(G)-nitro-L-arginine methyl ester-treated animals. Hence, blood flow-induced MMP activation is critical in flow-induced vascular enlargement and IEL fragmentation, and blood flow-induced nitric oxide participates in MMP activation.     

A calcium channel blocker, benidipine, inhibits intimal thickening in the carotid artery of mice by increasing nitric oxide production

OBJECTIVE: Recent studies suggest that several calcium channel blockers exert their protective effects against vascular disorders by increasing nitric oxide (NO) production from the endothelium. The purpose of this study was to clarify the effects of a long-lasting calcium channel blocker, benidipine, on vascular remodeling. METHODS: The left common carotid arteries of mice were completely ligated just proximal to the carotid bifurcation. Treatment with benidipine (3 mg/kg per day) or vehicle was started 1 week before the carotid ligation, and continued throughout the experiments. Four weeks after the carotid ligation, these mice were killed and vascular remodeling was analyzed. Moreover, NO production and endothelial NO synthase (eNOS) expression were assessed. RESULTS: At 4 weeks after ligation, the neointimal area in the vehicle-treated mice was 39,400 +/- 4,900 microm2 (n = 8), whereas that in the drug-treated mice was reduced to 18,300 +/- 3,800 microm2 (n = 10). Consequently, the luminal area was 35% larger in the drug-treated mice. Benidipine increased the basal as well as agonist-induced NO production from the endothelium, detected by Griess method or NOx analyzer. Endothelial NOS expression in vessels of the drug-treated mice was increased compared with that of the vehicle-treated mice. CONCLUSION: Our data provide evidence that benidipine increases NO production via increment of eNOS protein in vessels and prevents intimal thickening in mice. These results show the possibility of benidipine as a protective tool against vascular remodeling independent of its effect on blood pressure.     

Successful arterial embolization of arteriovenous fistula in the portal circulation.

We successfully performed arterial embolization of an arteriovenous fistula between the left gastric artery and vein. The increased blood flow in the portal vein via the left gastric vein and the arteriovenous fistula induced severe portal hypertension. After obliteration of the left gastric artery, the arteriovenous fistula was not opacified on angiography and the portal hypertension improved.     

Vasa vasorum neovascularization and lesion distribution among different vascular beds in ApoE-/-/LDL-/- double knockout mice

OBJECTIVE: To increase understanding of the substantial variation in the incidence and distribution of atherosclerotic lesions among different vascular beds. In view of some evidence that there are different distributions of adventitial vasa vasorum (VV) in different vascular beds, and that this correlates with lesion formation, we explored this possible linkage in apoE-/-/LDL-/- double knockout mice, which develop VV at age beyond 16 weeks. METHODS AND RESULTS: Samples from the aorta, coronary, pulmonary, carotid, and cerebral arteries in apoE-/-/LDL-/- double knockout mice at the age of 16-80 weeks (n=24) were scanned by micro-CT. Using those 3D images, we characterized plaque volume, vessel luminal diameter and VV luminal volume along the vessels. Results were complemented by histology. Advanced atherosclerotic lesions were found in the aorta, pulmonary artery and carotid artery. Occluded intramyocardial vessels (vessel diameter approximately 0.1mm) with concomitant myocardial infarctions were found without any evidence of adventitial VV neovascularization. VV luminal volume follows the order: aorta>pulmonary arteries>carotid arteries. VV were only observed in atherosclerotic diseased vessels with a lumen diameter>0.4mm. No atherosclerotic lesions, and no VV, were observed in cerebral arteries. CONCLUSION: The spatial heterogeneity in the development of atherosclerotic lesions among different vascular beds is linked to appearance of VV and to vessel lumen diameter.     

超声诊断创伤性动静脉瘘

目的:探讨彩色多普勒超声在创伤性动静脉瘘诊治中的应用价值。方法:回顾性分析10例创伤性动静脉瘘患者的灰阶和彩色多普勒超声图像,包括动静脉瘘瘘口发生位置、瘘口大小及形态、受累静脉增宽程度、动静脉内血流表现、动静脉瘘分流的血流峰值流速、受累动脉近心端和远心端的血流频谱变化,受累静脉内频谱表现,并与手术结果或磁共振对比。术后检查,注意观察动静脉瘘口是否闭合,瘘口处动静脉的灰阶图像及血流表现。结果:动静脉瘘超声定性诊断率100%(10/10),瘘口位置诊断准确率100%(10/10),血流频谱的特异性表现为瘘口处高速、低阻及双期单向连续性血流,受累静脉内出现动脉样频谱。术后检查瘘口闭合(9/9,100%),原受累静脉内未探及动脉样频谱。结论:多普勒超声诊断动静脉瘘具有无创、简便、易行且准确率较高的优点,并具有较高的临床应用价值。     

A new modified bovine heterograft for vascular access in haemophiliacs

Summary. Because of poor venous access and failure of previous arteriovenous shunts due to thrombosis, two patients with severe coagulapathies had an arteriovenous fistula performed using a new chemically treated bovine carotid artery segment (Solcograft-P). To date, no complications have been noted after 16 and 17 months respectively. This treated heterograft maintains many of the physical characteristics observed in a normal bovine carotid artery. The theoretical advantages for using this heterograft in such patients are discussed.     

前臂近端自体动静脉内瘘在老年血液透析病人中的应用

目的探讨老年血液透析病人在前臂近端建立自体动静脉内瘘的优劣性及临床转归。方法选取在我院进行首次自体动静脉内瘘建立的老年病人,分为近端组(桡动脉起始段与正中静脉或头静脉吻合)和远端组(桡动脉与头静脉吻合),观察2组病人内瘘术后的手术并发症以及内瘘血流量、成熟情况及预后等。结果所有内瘘手术术后即刻成功率为100%。术后6~8周进行内瘘超声评估,近端组和远端组的血流量分别为(1328.5±234.4)mL/min和(1125.6±198.1)mL/min(P<0.05),首次穿刺时间分别为(56±15)d和(62±13)d(P=0.03),首次穿刺成功率分别为87.8%和78.9%(P<0.05)。2组术后总体并发症发生率差异无统计学意义(P>0.05);所有手术6个月的总体通畅率为92.41%,1年的总体通畅率为81.01%。2组病人1年的内瘘存活率差异无统计学意义(85.2%比74.1%,P=0.32),但在第2年时,近端组的存活率为74.3%,明显高于远端组的48.3%(P<0.05);同时近端组由于血栓形成而导致的内瘘闭塞率及再次手术干预次数也低于远端组(P<0.05)。结论前臂近端自体动静脉内瘘具有成熟快、流量充足、通畅率高等优点,对于前臂远端血管条件不佳、需建立内瘘的老年人,尤其是高龄病人可以优先考虑。     

Circulation in neonates with intracranial arteriovenous fistula and cardiac failure

Two newborn infants with severe cardiac failure caused by a large cerebral arteriovenous communication were studied with complete cardiac catheterization, indicator-dilution curves and angiography. In one infant, studied at age 10 hours, a large right to left shunt through the patent ductus was seen with retrograde aortic flow into the left carotid artery. The entire flow in the descending aorta was supplied from the ductus. The second infant, studied at age 5 days, had a 20 percent right to left shunt through the foramen ovale and the ductus was closed. Hypoxia was caused by inadequate oxygenation of pulmonary venous blood, atrial right to left shunting and possibly ductal right to left shunting. The hemodynamic findings in cases of cerebral arteriovenous fistula would seem to depend on the patient's age at the time the studies are carried out and the severity of the lesion. Cardiac output was more than twice the normal value and blood flow through the arteriovenous fistula was probably greater than 4 liters/min per m².     

Apolipoprotein E polymorphism and atherosclerosis: association of the epsilon4 allele with defects in the internal elastic lamina

The defects in the internal elastic lamina (IEL) have been proposed to be important for the migration of smooth muscle cells into the intima during atherosclerosis. We investigated the association of a genetic factor--apolipoprotein E (apoE) genotype--with the number of gaps in the IEL of the artery wall in 123 consecutive autopsy cases (90 male, 33 female) aged 18-93. At autopsy, the circumference of the IEL and the number of gaps in the IEL were measured in circular samples of the coeliac; (CA), superior mesenteric (SMA) and inferior mesenteric (IMA) arteries. In the series, the number of gaps per millimetre in the IEL of CA, SMA and IMA were associated with intimal thickening (P<0.0001, P=0.01 and P=0.005, respectively). In men, apoE genotype was significantly associated with the number of gaps in the IEL of the CA and IMA (P=0.033 and P=0.041, respectively). The carriers of epsilon4/3 or epsilon4/4 genotype had higher number of gaps in CA than the carriers of epsilon3/3 genotype (2.30+/-2.63 vs. 1.38+/-1.83 gaps/mm, P=0.035) and also higher number of gaps in IMA than the carriers of epsilon3/2 (2.18+/-1.71 vs. 0.66+/-0.60 gaps/mm, P=0.041). The results suggest that the apoE varepsilon4 allele may be involved with IEL fragmentation in men. This may be mediated through higher serum cholesterol associated with the varepsilon4 allele.     

Endothelial NO synthase overexpression inhibits lesion formation in mouse model of vascular remodeling

NO produced by endothelial NO synthase (eNOS) plays important roles in the regulation of vascular tone and structure. The purpose of this study was to clarify the role of eNOS-derived NO on vascular remodeling by use of eNOS-transgenic (eNOS-Tg) mice. The common carotid artery was ligated just proximal to the carotid bifurcation. Four weeks later, the proximal carotid artery of the ligation site was histologically examined. In this vascular remodeling model, the endothelium remains uninjured, but neointimal and medial thickening occurs in combination with a reduction in vascular diameter at the proximal portion of the ligation. At 4 weeks after ligation, the respective neointimal and medial areas in wild-type mice were 17 200+/-1100 and 24 300+/-1500 microm(2), whereas both were reduced to 8000+/-1900 (P:<0.01) and 18 400+/-700 microm(2) (P:<0.01) in eNOS-Tg mice (n=8). Total vascular area was not different between the 2 genotypes. N:(G)-Nitro-L-arginine methyl ester treatment increased neointimal and medial areas to the same extent in both genotypes. Leukocyte infiltration was observed in the luminal side of the vessel, but the number of infiltrating cells was significantly attenuated in eNOS-Tg mice compared with wild-type mice. This reduction of leukocyte infiltration in eNOS-Tg mice was associated with reduced expressions of intracellular adhesion molecule-1 and vascular cellular adhesion molecule-1 on the endothelium. In conclusion, chronic eNOS overexpression in the endothelium reduced leukocyte infiltration and inhibited neointimal formation and medial thickening. Our data provide the evidence for the regulatory role of NO from the endothelium on vascular structure integrity.