NADPH氧化酶与Rho/Rho-激酶激活在外膜介导的血管重塑中的作用

目的　探讨NADPH氧化酶与Rho/Rho 激酶在外膜介导的血管重塑中的作用。方法在体去除兔颈动脉外膜 ,于术后即刻、1周及 2周取出颈动脉。用图像分析系统测定内膜及中层面积 ;应用多道生理仪测血管反应性 ;原位杂交及RT PCR检测mRNA表达。结果　 (1)血管外膜去除后内膜增生 ,2周时内膜增生较 1周时更为明显。对照侧无内膜增生。 (2 )与对照侧比较 ,去外膜侧血管在术后即刻、1周对去甲肾上腺素的收缩反应减弱 (P <0 0 5)。 (3 )与对照侧比较 ,去外膜侧NADPH氧化酶P2 2PhoxmRNA表达在 1周时增高 (P <0 0 5)。 (4)与对照侧比较 ,去外膜侧Rho 激酶mRNA表达在 2周时增高 (P <0 0 5)。结论　外膜去除后血管内膜增生 ,血管舒缩功能改变 ,其发生机制与NADPH氧化酶及Rho 激酶激活有关     

实验性血管外膜去除后高血压对血管内膜增殖和血管反应性的影响

本文观察外膜去除后升高血压对血管结构及功能的影响。实验采用在体去除兔颈动脉外膜方法，术后分对照组及高血压组(植入微型药物渗透泵恒量注入去甲肾上腺素)，分别于术后1周及2周后取出颈动脉。用图像分析系统测定内膜及中膜面积；应用多道生理仪测血管反应性；RT—PcR检测mRNA表达。结果 1)外膜去除后血管内膜增生，术后2周高血压组去外膜侧内膜面积／中膜面积较对照组增高(P＜0．05)；2)与完整侧比较，术后1周对照组去外膜侧血管对去甲肾上腺素(NE)的收缩反应减弱(P＜0．05)；而术后2周对照组与高血压组反应均增强(P＜0．05)。与对照组比较，术后1周及2周高血压组去外膜侧血管环反应增强(P＜0．05)。3)与对照组比较，术后2周高血压组去外膜侧Rho-A mRNA表达及MCP-1表达较对照组增高(P＜0．05)。术后2周对照组及高血压组去膜侧Rho-Ki-nase mRNA表达较完整侧上调(P＜0．05)；术后1周高血压组完整侧及去外膜侧Rho-Kinase mRNA表达较对照组上调(P＜0．05)，2周时上调更明显(P＜0．01)。术后2周高血压组去外膜侧MCP-1mRNA表达较完整侧上调(P＜0．05)；术后2周高血压组完整侧及去外膜侧MCP-1mRNA表达明显上调(P＜0．01)。结论 高血压可加局外膜去除后的血管内膜增生程度及血管收缩性，其机制涉及Rho-Kinase及MCP-1的激活。     

实验性血管外膜去除后高血压对血管内膜增殖和血管反应性的影响

本文观察外膜去除后升高血压对血管结构及功能的影响.实验采用在体去除兔颈动脉外膜方法,术后分对照组及高血压组(植入微型药物渗透泵恒量注入去甲肾上腺素),分别于术后1周及2周后取出颈动脉.用图像分析系统测定内膜及中膜面积;应用多道生理仪测血管反应性;RT-PCR检测mRNA表达.结果 1)外膜去除后血管内膜增生,术后2周高血压组去外膜侧内膜面积/中膜面积较对照组增高(P<0.05);2)与完整侧比较,术后1周对照组去外膜侧血管对去甲肾上腺素(NE)的收缩反应减弱(P<0.05);而术后2周对照组与高血压组反应均增强(P<0.05).与对照组比较,术后1周及2周高血压组去外膜侧血管环反应增强(P<0.05).3)与对照组比较,术后2周高血压组去外膜侧Rho-A mRNA表达及MCP-1表达较对照组增高(P<0.05).术后2周对照组及高血压组去外膜侧Rho-Kinase mRNA表达较完整侧上调(P<0.05);术后1周高血压组完整侧及去外膜侧Rho-Kinase mRNA表达较对照组上调(P<0.05),2周时上调更明显(P<0.01).术后2周高血压组去外膜侧MCP-1 mRNA表达较完整侧上调(P<0.05);术后2周高血压组完整侧及去外膜侧MCP-1 mRNA表达明显上调(P<0.01).结论高血压可加剧外膜去除后的血管内膜增生程度及血管收缩性,其机制涉及Rho-Kinase及MCP-1的激活.     

自发性高血压大鼠一侧颈动脉去外膜后血管内膜增生及阿托伐他汀的干预作用

目的研究自发性高血压大鼠(SHR)一侧颈动脉外膜去除后血管内膜增生及阿托伐他汀的干预作用。方法24只13周龄雄性SHR去除右侧颈动脉外膜后,随机分为3组(每组8只),分别为SHR组、阿托伐他汀组、缬沙坦组;8只同周龄雄性WKY大鼠作为正常血压对照组(WKY组)。机械和化学方法去除大鼠右侧颈动脉外膜,左侧作假手术对照。4周后,放免法测定血浆及双侧颈动脉血管紧张素Ⅱ(AngⅡ)浓度,取双侧颈动脉制成光镜标本,病理图像分析系统测颈动脉管腔横截面积(LA)、内弹力层围绕面积(IELA)、外弹力层围绕面积(EELA),评价内膜和中膜增生程度。RT—PCR法检测颈动脉血管紧张素转换酶2 mRNA(ACE2 mRNA)表达,免疫组化法检测ACE2 mRNA、蛋白激酶C-ζ(PKC-ζ)和胞外信号调节激酶1／2(ERKl／2)蛋白表达。结果(1)与WKY组比较,SHR组双侧血管内膜明显增生(P<0．01),中膜面积显著增大[分别为(0．0240±0．0074)mm2和(0．0160±0．0052)mm2,P<0．05;(0．0250±0．0054)mM2和(0．0190±0．0035)mm2, P<0．01)],去外膜侧内膜增生较外膜完整侧显著(P<0．05);与SHR组比较,阿托伐他汀组内膜增生不显著(P<0．01);(2)与外膜完整侧比较,去外膜侧颈动脉AngⅡ浓度和PKC-ζ、ERK1／2蛋白表达均显著增高(P<0．01),ACE2 mRNA和蛋白表达均明显降低(P<0．01);与SHR组比较,阿托伐他汀组颈动脉AngⅡ浓度及PKC-ζ、ERK1／2蛋白表达显著降低(P<0．01),血浆AngⅡ浓度、ACE2 mRNA和蛋白表达显著升高(P<0．01)。结论SHR去除一侧颈动脉外膜后血管内膜增生明显,中膜面积增大,阿托伐他汀可显著改善这种改变。     

血管紧张素(1-7)对颈动脉去外膜后内膜和中膜增生的影响

目的 研究血管紧张素(1～7)[Ang(1～7)]对自发性高血压大鼠(SHR)一侧颈动脉外膜去除后血管内膜增生的影响.方法 13周龄雄性SHR 24只去除右侧颈动脉外膜后,随机分为3组(每组8只):SHR对照组、Ang(1～7)组(25 μg/kg·h)和Ang(1～7)拮抗剂(Ang 779)组(25 μg/kg·h);8只同周龄雄性WKY大鼠作为正常血压对照组(WKY组).机械和化学方法去除大鼠右侧颈动脉外膜,左侧作假手术对照.采用微渗泵植入技术经颈静脉给药2周,鼠尾袖法测量尾动脉收缩压(SBP),放免法测定血浆及双侧颈动脉血管紧张素Ⅱ(Ang Ⅱ)浓度.取双侧颈动脉制成光镜标本,病理图像分析系统测定颈动脉管腔横截面积(LA)、内弹力层围绕面积(IELA)、外弹力层围绕面积(EELA),评价内膜和中膜增生状况.免疫组织化学方法测定双侧颈动脉血管紧张素Ⅱ 1型受体(AT 1R)蛋白、蛋白激酶C-ζ(PKC-ζ)和胞外信号调节激酶1/2(ERK 1/2)蛋白表达.结果 Ang (1～7)明显降低SBP(P＜0.01),与SHR对照组和Ang 779组去外膜侧颈动脉内膜增生比较,Ang (1～7)明显改善因去外膜后引起的血管内膜增殖(P＜0.01).虽然Ang (1～7)未能减少去外膜后颈动脉壁的Ang Ⅱ浓度,但能明显降低颈动脉AT1R蛋白表达(P＜0.01)和减少因去外膜后引起的管壁PKC-ζ及ERK1/2蛋白表达(P＜0.01).结论 Ang(1～7)可显著抑制SHR去外膜后颈动脉的内膜增生,这一作用可能是其通过下调颈动脉AT 1R和减少PKC-ζ及ERK1/2蛋白表达而实现的.     

阿托伐他汀对自发性高血压大鼠去外膜颈动脉内膜增生的影响

目的研究阿托伐他汀对自发性高血压大鼠颈动脉外膜去除后血管内膜增生的影响。方法24只13周龄雄性自发性高血压大鼠去除右侧颈动脉外膜后,随机分为自发性高血压组、阿托伐他汀组和缬沙坦组,每组8只;8只同周龄雄性WKY大鼠作为正常对照组。机械和化学法去除大鼠右侧颈动脉外膜,左侧作假手术对照。4周后,放射免疫法测定血浆及双侧颈动脉血管紧张素Ⅱ浓度,取双侧颈动脉制成光镜标本,病理图像分析系统测定颈动脉管腔横截面积、内弹力层围绕面积、外弹力层围绕面积,评价内膜和中膜增生程度。逆转录聚合酶链反应检测颈动脉血管紧张素转化酶2 mRNA表达,免疫组织化学法检测血管紧张素转换酶2蛋白表达。结果自发性高血压大鼠对照组去外膜侧和外膜完整侧血管内膜增生较正常对照组明显(P<0.01),中膜面积显著增大(P<0.05或P<0.01),去外膜侧内膜增生较外膜完整侧显著(P<0.05);阿托伐他汀组较自发性高血压组内膜增生显著降低(P<0.01)。与外膜完整侧比较,去外膜侧颈动脉血管紧张素Ⅱ浓度显著增高(P<0.01),血管紧张素转化酶2mRNA和蛋白表达明显减弱(P<0.01);与自发性高血压组比较,阿托伐他汀组颈动脉血管紧张素Ⅱ浓度显著降低(P<0.01),血浆血管紧张素Ⅱ浓度、血管紧张素转化酶2 mRNA和蛋白表达显著升高(P<0.01)。结论阿托伐他汀可显著抑制自发性高血压大鼠颈动脉去外膜后血管内膜增生,其机制可能是通过上调血管局部血管紧张素转化酶2而实现的。     

血管紧张素(1-7)对颈动脉去外膜后内膜和中膜增生的影响

目的研究血管紧张素(1～7)[Ang(1～7)]对自发性高血压大鼠(SHR)一侧颈动脉外膜去除后血管内膜增生的影响。方法13周龄雄性SHR24只去除右侧颈动脉外膜后,随机分为3组(每组8只):SHR对照组、Ang(1～7)组(25μg/kg.h)和Ang(1～7)拮抗剂(Ang779)组(25μg/kg.h);8只同周龄雄性WKY大鼠作为正常血压对照组(WKY组)。机械和化学方法去除大鼠右侧颈动脉外膜,左侧作假手术对照。采用微渗泵植入技术经颈静脉给药2周,鼠尾袖法测量尾动脉收缩压(SBP),放免法测定血浆及双侧颈动脉血管紧张素Ⅱ(AngⅡ)浓度。取双侧颈动脉制成光镜标本,病理图像分析系统测定颈动脉管腔横截面积(LA)、内弹力层围绕面积(IELA)、外弹力层围绕面积(EELA),评价内膜和中膜增生状况。免疫组织化学方法测定双侧颈动脉血管紧张素Ⅱ1型受体(AT1R)蛋白、蛋白激酶C-ζ(PKC-ζ)和胞外信号调节激酶1/2(ERK1/2)蛋白表达。结果Ang(1～7)明显降低SBP(P<0.01),与SHR对照组和Ang779组去外膜侧颈动脉内膜增生比较,Ang(1～7)明显改善因去外膜后引起的血管内膜增殖(P<0.01)。虽然Ang(1～7)未能减少去外膜后颈动脉壁的AngⅡ浓度,但能明显降低颈动脉AT1R蛋白表达(P<0.01)和减少因去外膜后引起的管壁PKC-ζ及ERK1/2蛋白表达(P<0.01)。结论Ang(1～7)可显著抑制SHR去外膜后颈动脉的内膜增生,这一作用可能是其通过下调颈动脉ATR和减少PKC-ζ及ERK1/2蛋白表达而实现的。     

血管外膜剥离致内膜增生病变的动物模型

目的建立颈动脉外膜剥离引起内膜增生的动物模型,为研究血管外膜在动脉粥样硬化发生中的作用奠定基础。方法2g/L的Ⅱ型胶原酶消化颈动脉外膜后,眼科镊钝性剥离外膜,HE染色明确外膜剥离效果;免疫组织化学染色观察外膜剥离对内膜的影响。结果酶化学消化 眼科镊钝性剥离可有效剥离血管外膜;外膜剥离2周后可见相应内膜处出现增生性病变,病变成分为分泌型平滑肌细胞;而外膜保留侧正常。结论胶原酶消化 眼科镊钝性剥离的方法可有效剥离血管外膜,促进血管内膜增生性病变形成。     

通心络对血管外膜损伤后氧化应激反应及内膜病变的作用

目的:探讨通心络对血管外膜损伤后内膜病变的作用及机制。方法: 纯种高血脂新西兰大白兔18只,采用胶原酶消化＋钝性机械分离的方法建立兔颈动脉外膜损伤模型后,随机分为对照组、通心络组和阿托伐他汀组,对照组给予盐水灌胃,另两组分别给予通心络和阿托伐他汀进行干预,共12周。采用HE染色法检查外膜损伤血管的形态变化,用免疫组化染色法测定血管组织中α-actin、CD68及Ⅰ、Ⅲ型胶原蛋白的表达;用实时荧光定量PCR(real-time quantitative PCR,RQ-PCR)技术检测外膜损伤后血管组织中NADPH氧化酶亚单位p22phox mRNA的表达。结果: 与对照组比较,通心络和阿托伐他汀均可显著抑制内膜病变的形成,并明显增加病变中α-actin及Ⅰ、Ⅲ型胶原蛋白的表达(P<0.05),抑制p22phox mRNA的表达(P<0.05)。结论: 通心络及阿托伐他汀均可有效地抑制血管外膜损伤后内膜病变的形成,并增加病变的稳定性,抗氧化应激可能是两种药物作用的机制。     

全反式维甲酸对兔颈动脉粥样硬化病变中Cdk2表达及血管平滑肌细胞增生的影响

目的探讨全反式维甲酸(ATRA)对兔颈动脉粥样硬化病灶中血管内膜的增生、血管平滑肌细胞(VSMCs)增殖、增殖细胞核抗原(PCNA)及细胞周期素依赖性激酶Cdk2表达规律的影响。方法36只新西兰雄性大白兔随机分为3组:正常饮食组、手术组、ARTA治疗组,每组12只。手术组和治疗组均给予高脂饮食,两周后用空气干燥法制作颈动脉内膜损伤模型,治疗组于术前3d开始给予ATRA灌胃。于术后1、4周处死动物,取病变血管应用HE染色、免疫组化和计算机图像分析法进行形态学、PCNA和Cdk2表达水平的检测。结果①正常动脉壁未见PCNA及Cdk2表达。②手术组在术后第1周时内膜开始增生,第4周增生明显,且出现泡沫细胞、脂质核心形成、管腔狭窄;增生内膜中Cdk2表达水平增高。③治疗组Cdk2的表达明显低于手术组(P<0.05),VSMCs的迁移、增殖、内膜增生和管腔狭窄显著减轻(P<0.05)。④PCNA表达与Cdk2表达呈显著正相关(P<0.01)。结论ARTA可通过抑制Cdk2表达,抑制VSMCs的迁移和增殖,从而抑制兔颈动脉粥样硬化新生内膜过度增生和管腔狭窄。     

Intravascular ultrasound imaging of arterial wall architecture

Intravascular ultrasound (IVUS) is a promising new technique for assessing vascular morphology and structure. Controversy exists whether the three-layer appearance of the arterial wall correctly reflects the histologic structures of the intima, media, and adventitia. We performed an experimental study to clarify the three-layer appearance. The vessel wall architecture was analyzed by IVUS on eight different kinds of plastic cylinders, 24 normal blood vessels from pigs, and 59 human arterial segments. A distinct three-layer appearance was observed on all the plastic cylinders when the ultrasound beam was perpendicular to the wall. A three-layer appearance was also seen in the arterial wall, in the muscular (iliac, femoral artery) and elastic types (aorta), when the echo beam was perpendicular to the vessel wall. The three-layer pattern was even observed on the arterial wall when the intima was removed. Furthermore, the removed intima itself provided a three-layer image. Histologic examination showed that there was no correspondence between the IVUS three-layer appearance and the intima, media, and adventitia. Moreover, we also performed IVUS on nine patients who suffered from aortic dissection. Intravascular ultrasonic visualization of the dissected intima showed a distinct three-layer pattern. The pattern disappeared when: (1) the echo beam was not perpendicular to the vessel wall; (2) there was connective tissue around the vessel wall; (3) there was arterial wall calcification; or (4) the vessel wall was too thick or the distance between the ultrasound transducer and the vessel wall was too large.(ABSTRACT TRUNCATED AT 250 WORDS)     

SPARC gene expression is increased in diabetes-related mesenteric vascular hypertrophy

The anti-adhesive extracellular matrix protein SPARC (secreted protein and rich in cysteine; osteonectin or BM-40) has been implicated in the regulation of matrix turnover, cell migration, and proliferation. The present study sought to examine whether modulation in the expression of this protein may play a role in diabetes-associated vascular remodeling. SPARC mRNA and protein were measured in mesenteric vessels of diabetic rats and controls. Hypertrophy of mesenteric vessels was noted after 3 and 32 weeks of diabetes as revealed by the increase in mesenteric vessel wet weight and an increased wall/lumen ratio. SPARC mRNA was sparsely present in intima and adventitia of control vessels. There was a marked increase in SPARC gene expression in the intima and adventitia of mesenteric vessels after 1, 3, and 32 weeks of diabetes. SPARC protein was demonstrated in the vessel wall in control animals and was increased in the mesenteric vessels of diabetic rats after 1 and 32 weeks of diabetes. Administration of the inhibitor of advanced glycation end-product formation, aminoguanidine, to diabetic rats attenuated both the hypertrophic response in mesenteric vessels and the overexpression of SPARC mRNA and protein without affecting glycemic control or food intake. In summary, diabetes-related mesenteric vascular hypertrophy is associated with an increase in SPARC expression in the vessel wall. The modulation of SPARC expression in mesenteric vessels of diabetic rats might be of pathogenetic significance in the development of vascular remodeling in diabetes.     

血管成形术后血管外膜改变与血管重塑的相关性研究

目的:探讨大鼠胸主动脉血管成形术后血管外膜激活与血管重塑的相关性。方法:用6F人冠状动脉快速交换球囊损伤大鼠胸主动脉,术后2周和6周取材,行血管形态学定量分析,并行增殖细胞核抗原(PCNA)免疫组织化学染色,观察PCNA在血管外膜上的表达。结果:血管成形术组血管外膜细胞数量、血管外膜细胞增殖指数,外膜面积、厚度均较对照组显著增大(P<0.05),血管外弹力板围绕面积、内弹力板围绕面积和管腔面积较对照组显著减小(P<0.05),血管呈收缩性重塑。结论:血管成形术后,血管外膜被牵拉激活,导致外膜细胞分裂、增殖,以及血管收缩性重塑,参与再狭窄的发生。     

Migration of mononuclear cells expressing β-actin through the adventitia into media and intima in coronary arteriogenesis and venogenesis in ischemic myocardium

It was previously thought that arteriogenesis and venogenesis are induced not only by proliferation of vessel-resident smooth muscle cells (SMCs) and endothelial cells (ECs) but also by migration of their precursors. However, it is not well understood through what route(s) the precursors migrate into the existing vessels.We examined through what route or routes circulating mononuclear cells expressing β-actin (β-MNCs), which we identified in canine coronary vessels, migrate into coronary vessel walls and cause arteriogenesis and venogenesis at 1, 2, 4 and 8 weeks after induction of myocardial infarction.The following changes were observed: (1) The β-MNCs migrated via coronary microvessels to the interstitial space at one week; (2) β-MNCs traversed the adventitia into the media and settled in parallel with pre-existing smooth muscle cells (SMCs) in arterioles and arteries and lost β-actin and acquired α-smooth muscle actin (α-SMA) to become mature SMCs at 2-4 weeks; (3) at the same time, other β-MNCs migrated across the adventitia and media into the intima and settled in parallel with pre-existing endothelial cells (ECs) and lost β-actin, while acquiring CD(31), to become mature ECs, resulting in arteriogenesis; (4) Similarly, β-MNCs migrated into venular and venous walls and became SMCs or ECs, resulting in venogenesis.β-MNCs in the interstitial space expressed CD(34) but not other major vascular cell markers.β-MNCs, possibly a vascular progenitor, migrate not from the lumen but across the adventitia into the media or intima of coronary vessels and transit to SMCs or ECs, and participate in arteriogenesis and venogenesis in ischemic myocardium.     

2型糖尿病血管病变与内皮功能关系的研究

目的:观察2型糖尿病(DM)无(A组)与有(B、C组)血管病变者的血管内皮功能。方法:121例2型DM患者被随机分为A、B、C3组,A组不伴有血管病变,42例;B组伴有微血管病变,39例;C组伴大血管病变,40例。另设健康对照组,40例。测定各组的血浆血栓调节蛋白(thrombomodulin,TM)、内皮素-1(ET-1)、血管性假血友病因子(vWF)的含量,并与正常对照组比较。结果:TM在A、B、C组均高于对照组(P<0.05),B、C组又高于A组,差异有显著意义(P<0.05)。ET-1、vWF水平在B、C组高于对照组及A组,差异有显著意义(P<0.05)。结论:DM在血管并发症出现前已存在血管内皮功能的损伤,随着血管病变的发生内皮功能损伤更加明显。     

Adventitial application of the NADPH oxidase inhibitor apocynin in vivo reduces neointima formation and endothelial dysfunction in rabbits

OBJECTIVE: Reactive oxygen species including superoxide have been shown to promote atherogenesis. We previously showed that a major source of superoxide, the NADPH oxidase system, is upregulated in the intima and adventitia during remodelling induced by periarterial collars in rabbits. We have now examined the action of the NADPH oxidase inhibitor apocynin, given via the adventitia, on the neointima formation and endothelial function in this model. METHODS: Perivascular collars were implanted around the common carotid arteries of male NZW rabbits for 14 days to induce intimal thickening. The periarterial space of one collar was filled with apocynin (1 mM) while the contralateral collar with the vehicle (0.1% DMSO). RESULTS: After 14 days, local treatment with apocynin via the adventitia, reduced superoxide generation. In addition, apocynin significantly reduced neointima formation and proliferation of cells in both the neointima and adventitia. Moreover, NO-dependent vasorelaxation to acetylcholine, which is normally impaired in collared arteries, was improved, and apocynin suppressed the endothelial expression of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1. CONCLUSIONS: NADPH oxidase is implicated in vascular remodelling and superoxide-stimulated cell proliferation in the neointima contributes to intimal hyperplasia in this collar model. Targeting NADPH oxidase via adventitial drug delivery not only reduces superoxide generation, but also normalises endothelial cell function. Targeting the primary source of NADPH oxidase-derived superoxide is an effective approach to prevent deleterious arterial remodelling, providing a rationale for designing more efficacious and selective inhibitors of vascular NADPH oxidase as potential therapeutics for human vascular disease.     

Arterialization of human vein grafts is associated with tenascin-C expression.

OBJECTIVES: This study was performed to test the hypothesis that tenascin-C (TN-C), an extracellular matrix (ECM) protein with counteradhesive chemotactic and vascular growth-promoting effects, is expressed in "arterialized" human saphenous vein grafts (SVGs). BACKGROUND: Tenascin-C is expressed in the vessel wall after vascular injury in the experimental model, where it has been implicated in the formation of neointima. Overexpression of TN-C has also been implicated in the development and progression of pulmonary hypertension. Saphenous vein grafts are exposed to hemodynamic stress when interposed in the arterial circulation and mechanical stress upregulates expression of TN-C, whereas stress-relaxation suppresses its synthesis. We hypothesized that the hemodynamic stress of increased arterial pressure could also induce TN-C expression in SVG. METHODS: We examined the expression of TN-C protein and mRNA in normal vein and "arterialized" human SVG using immunohistochemistry and in situ hybridization, respectively. RESULTS: TN-C protein was not detected in control human saphenous veins; however, it was uniformly and strongly expressed in the adventitia and media of patent human vein grafts, with minimal or no expression in the neointima (n = 27, 100%). In situ hybridization showed that TN-C mRNA was not detected in the neointima, but was strongly upregulated in the adventitia and media, corroborating immunostaining data (n = 10, 100%). Unlike patent SVG, TN-C was not expressed in the adventitia of occluded grafts, except for a low level of expression around the newly formed vessels in neointima (n = 5, 100%). Smooth muscle cell-specific staining demonstrated that the lack of expression of TN-C in occluded vein grafts is not due to the lack of presence of smooth muscle cells in the graft. CONCLUSIONS: These findings suggest that placement of a venous graft in the arterial system leads to expression of TN-C, which may in turn facilitate graft remodeling. Conversely, loss of flow and intravascular pressure, associated with vein graft occlusion, is accompanied by disappearance of TN-C expression.     

Myofibroblast-mediated adventitial remodeling: an underestimated player in arterial pathology

The arterial adventitia has been long considered an essentially supportive tissue; however, more and more data suggest that it plays a major role in the modulation of the vascular tone by complex interactions with structures located within intima and media. The purpose of this review is to summarize these data and to describe the mechanisms involved in adventitia/media and adventitia/intima cross-talk. In response to a plethora of stimuli, the adventitia undergoes remodeling processes, resulting in positive (adaptive) remodeling, negative (constrictive) remodeling, or both. The differentiation of the adventitial fibroblast into myofibroblast (MF), a key player of wound healing and fibrosis development, is a hallmark of negative remodeling; this can lead to vessel stenosis and thus contribute to major cardiovascular diseases. The mechanisms of fibroblast-to-MF differentiation and the role of the MF in adventitial remodeling are highlighted herein.