Death of Smooth Muscle Cells and Expression of Mediators of Apoptosis by T Lymphocytes in Human Abdominal Aortic Aneurysms

Abstract

Background-Thinning of the tunica media and rarefaction of smooth muscle cells (SMCs) characterize aneurysmal aortas. Apoptosis determines the cellularity and morphogenesis of tissue. Macrophages and T lymphocytes infiltrate the wall of abdominal aortic aneurysms (AAAs) and produce death-promoting proteins (perforin, Fas, and FasL). This study investigated whether apoptosis occurs in association with the expression of these proteins. Methods and Results-We examined signs of apoptosis and expression of death-promoting mediators in segments of AAAs from patients undergoing elective repair (nϭ20). Anti-␣-actin immunostaining showed a reduced number of SMCs in AAAs. In situ terminal transferase-mediated dUTP nick end-labeling (TUNEL) showed higher levels of DNA fragmentation in AAAs than in controls (nϭ5). The AAA walls contained more cells bearing markers of apoptosis than normal aorta (PϽ0.05, Student's t test). Double immunostaining identified SMCs and macrophages as the principal cell types displaying fragmented DNA. Immunohistochemistry revealed that AAAs but not normal aorta contained CD4

In Vitro and Pilot In Vivo Evaluation of a Bioactive Coating for Stent Grafts Based on Chondroitin Sulfate and Epidermal Growth Factor

“…Additionally, the vein patch used in this study provides a geometrical aneurysm model, one with realistic flow conditions; however, this model is exempt of atherosclerosis and calcium deposits, it displays normal ECM, without inflammation and SMC depletion, unlike a real AAA [3].…”

“…This can be related to three main factors: (i) the pro-apoptotic environment of a diseased aneurysmal vessel, characterized by changes in extracellular matrix composition, presence of inflammatory cells, vascular cell depletion [3,4]; (ii) the lack of oxygen and nutrients after SG insertion; and (iii) the nature of the materials used for SG cover, namely polyethylene terephtalate (PET) or poly(tetrafluoroethylene) (PTFE). The deficit of tissue formation on the SG abluminal side could play a role in the occurrence of type I endoleaks and endotension (defined by a sac enlargement of more than 5mm without visible leak) that affect respectively 13 and 18 % of patients treated by SG.…”

VPO1 Modulates Vascular Smooth Muscle Cell Phenotypic Switch by Activating Extracellular Signal‐regulated Kinase 1/2 (ERK 1/2) in Abdominal Aortic Aneurysms

“…The phenotypic switch is characterized by VSMC dedifferentiation and migration into the neointima. VSMC phenotypic switch is an important first step in AAA formation and is marked by a loss of smooth muscle cell (SMC) gene expression, an increase in matrix metalloproteinases (MMPs) and extracellular matrix synthesis, as well as enhanced VSMC proliferation 2, 3. The precise mechanism for VSMC phenotypic switch, however, is not well understood.…”

Inhibition of Transforming Growth Factor β Worsens Elastin Degradation in a Murine Model of Kawasaki Disease

“…However, collagen synthesis, as judged by mRNA expression, was not greater in the group treated with LCWE plus TGF-␤ compared with those treated with LCWE plus IgG, suggesting that other matrix components (eg, fibronectin or osteopontin) predominated in this constrictive remodeling response, similar to that seen in the adventitial fibrosis that occurs after other types of vascular injury. 51 Furthermore, although loss of elastin is an early feature of aneurysm formation, recent evidence suggests that other factors are likely required for the vessel dilation that occurs in aneurysm formation, including apoptosis of vascular smooth muscle cells 52 and alterations in smooth muscle cell contractile proteins. 53 It is also possible that a transient phase of coronary dilation preceded the constrictive remodeling observed in the LCWE-treated mice, similar to that seen in the clinical setting.…”