Adventitia and Arterial Lesion
Intimal injury
Media SMC migration and proliferation
Adventitia: An innocent bystander or an active participant
The adventitia is derived from the Latin adventicius, or "coming from abroad, foreign", given its "outsider" status.
Adventitia is composed primarily of fibroblasts, collagen, and elastin fibers.
It provides support for the blood vessel (extracellular matrix) and a scaffold for sympathetic nerve endings and the vasa vasorum.
The role of the adventitia in vascular function and vascular lesion formation has been largely ignored,.
I. Adventitia and atherosclerosis
II. Adventitial fibroblasts and
angioplasty
I. Adventitia and atherosclerosis
1. The adventitia is activated during the development of atherosclerosis.
2. There is a positive relationship between the degree of adventitial inflammation and the severity of atherosclerotic disease in the overlying arterial wall.
3. Adventitial inflammation is an early event in the development of arterial lesion.
Inflammatory cells were decribed in the adventitia surrounding atherosclerotic arteries by Albuti in 1915
Schwartz and Mitchell did a study in 1962 of over 440 tissue blocks from 111 randomly selected men and women over 35 years of age.
1. The adventitia is activated during the development of atherosclerosis.
In 1980s, studies identified the adventitial inflammatory cells asscociated with atherosclerotic development as being
55% B cells,
35% T cells and
10% macrophages,
IgG and IgM were also localized in chronic periaortitis.
(1990s) Apo E-deficient mice for study of mechanisms of formation of AS lesions.
Loss of lumen did not correlate with lesion mass but did correlate with adventitial inflammation and medial atrophy.
衣原体
臂动脉
（衣原体）
肺炎衣原体
Vascular-associated lymphoid tissue (VALT) involvement in aortic aneurysm
A：Massive inflammatory infiltration
(*:AS necrotic core. M: media. A: adventitia)
C: Massive inflammatory infiltration
B+D: CD3 positive cells (rose) in adventitia of AAA wall. (T-cell)
A: T-cells (rose)
Dendritic cells (S-100+，brown)
B: detail of A
The toll-like receptor 4 (TLR4) is the receptor for bacterial lipopolysaccharides and also recognizes cellular fibronectin and heat shock protein 60, endogenous peptides that are produced in response to tissue injury.
TLR4 expression in cells in adventitia of human atherosclerotic coronary artery (TLR4: blue, macrophage: red, IHC)
Open arrow indicates double- stain cells (macrophages expressing TLR4).
Double-immunofluorescence staining of primary human adventitial fibroblasts
a. TLR4,
b. vimentin,
c. western blot for TLR4 detection).
Circulation. 2001;104:2228
Perivascular Inflammation After Balloon Angioplasty of Porcine Coronary Arteries
2 hours after angioplasty
A.Localization of P-selectin mRNA in ECs of adventitial vasa
vasorum,.
B. P-selectin protein (IHC)
C. E-selectin mRNA
D.VCAM-1 mRNA
3 days after angioplasty
Localization of P-selectin mRNA in adventitia ( protein in similar distribution)
B. Localization of P-selectin mRNA in lumen
C+D. E-selectin; E+F. VCA-1
Experimental adventitial inflammation(1)
(1989)Adventitial inflammation was induced by placing an endotoxin-soaked thread in the adventitia along the rat femoral artery.
Leukocyte (neutrophils and mononuclear cells) migration into the vessel occurred from both the lumenal and adventitial sides.
Cytokines may also be released by the leukocytes which remain in the adventitia and be carried into the vessel wall by the vasa vasorum where they may also play a role in activation of the medial SMC.
One week later, smooth muscle-rich vascular lesions were found on the lumenal surface adjacent to the region where the thread was placed.
2004(AS杂志)脂多糖诱导的血管外膜炎症对兔股动脉内膜增生的影响及机制
结果提示脂多糖诱导的血管外膜炎症可导致兔股动脉内膜增生,而在内膜增生之前伴随着血管内皮细胞和外膜细胞核因子κBp65的阳性表达,外膜炎症可能是通过激活上述细胞中的核因子κB从而启动炎性细胞因子的转录导致内膜增生。
Experimental adventitial inflammation(2)
(1994)Removal of the carotid artery adventitia from rabbits induced the formation of an intimal hyperplastic lesion. Electron microscopy and immunocytochemistry showed two types of lesion:
(a) smooth muscle cell predominant on normal diet (b) macrophage predominant on high cholesterol diet.
Lesion formation may be initiated following the development of arterial wall hypoxia, secondary to excision of the adventitial vasa vasorum.
牟华明(重庆，2003)
(1)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
(2)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
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。
结论:(1)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。
(2)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 (还原型辅酶II）氧化酶及Rho 激酶激活有关.
Those evidences indicate that adventitia is not an innocent bystander, but an active participant.
2. There is a positive relationship between the degree of adventitial inflammation and the severity of atherosclerotic disease in the overlying arterial wall, and is often found associated with necrosis or thinning of the medial wall.