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Objectives: In-stent restenosis due to neointima formation is a major limitation following stent implantation. Recently, several studies reported mobilization of primarily extravascular cells to the arterial sites after balloon angioplasty. Therefore, the goal of the present study was to assess the coordinated neointimal expression of endothelial progenitor, dendritic and neural crest-derived cells after stent implantation., Methods: Male minipigs underwent stent implantation in abdominal aortic segments. Animals were sacrificed at 1, 7, 14, 30, 60 or 90 days. Cross sections of the injured vessels were obtained for immunohistochemistry using specific antibodies for the detection of endothelial progenitor (CD133), dendritic (S100) and neural crest-derived cells (GFAP), as well as monocytes/macrophages (CD14) and T lymphocytes (CD3)., Results: As a key finding, frequency of CD133, S100, GFAP, CD14 and CD3 (18.5 +/- 3.6, 14.9 +/- 1.8, 10.6 +/- 1.1, 40.2 +/- 8.3 and 5.0 +/- 0.6%, respectively) in neointima was maximal at day 7. With ongoing neointima enlargement, expression of these cells decreased. In advanced neointima, labeled cells were predominantly localized at luminal and stented sites. Media showed almost no immunoreactivity of the markers studied, whereas adventitial zones of neovascularization revealed some signals., Conclusions: Endothelial progenitor, dendritic, neural crest-derived and inflammatory cells are consistently recruited into arterial neointima, mostly at early time points after stent implantation., ((c) 2007 S. Karger AG, Basel.)

The long-term pathomorphological changes of the injured vessels under angiotensin-converting-enzyme (ACE) inhibitor are still not known. Therefore, we assessed the alternations of vascular architecture after three-month therapy with ACE inhibitor and identified new target cells for this medication. Carotid arteries of spontaneously hypertensive rats underwent balloon angioplasty. 14 days prior intervention, half of the animals was treated with ACE inhibitor. After three months of vascular trauma, the injured vessels were explored by histomorphology and immunohistochemistry for angiotensin-II receptor (AT1R), dendritic and HSP47+ cells. The neointimal growth decreased significantly only up to 28 days under ACE inhibitor. In contrast, the reductive effect of ACE inhibitor on media area persisted up to three months after intervention. A significant fraction of early neointimal cells was of a dendritic cell type. The relevant portion of these cells showed an expression of AT1R and HSP47. AT1R was present in 70% and HSP47 in 18% of all early neointimal cells in both groups. ACE inhibitor may at least temporarily diminish remodelling processes in injured vessels. The detection of AT1R on dendritic cells identifies these cells as important targets for therapeutic strategies involving modulation of the renin-angiotensin system. [ABSTRACT FROM AUTHOR]

Abstract: Background: Increased proliferation, mitigated apoptosis, and recruitment of primarily extravascular cells to injured vessels are important processes during neointima formation. Therefore, the goal of this study was to assess the spatiotemporal balance between proliferation and apoptosis and the influence of apoptosis on the survival of primarily extravascular cells in in-stent neointima. Methods: Minipigs underwent stent implantation to abdominal aortic segments. At Days 1, 7, 14, 30, 60, and 90 after injury, arterial cross sections were analyzed by TUNEL assay to detect apoptotic cells. For immunohistochemical detection of Ki67+/proliferating cell nuclear antigen (PCNA)+ proliferative, caspase3+ apoptotic, S100+/fascin+ dendritic, GFAP+ neural crest-derived cells and CD14+ monocytes/macrophages, the alkaline phosphatase–anti-alkaline phosphatase (APAAP) method was used. Results: In the incipient cell-rich neointima, both frequency of proliferation and apoptosis was maximal (Ki67, 28.5±2.2%; PCNA, 25.4±3.8%; TUNEL, 8.6±0.4%; caspase3, 7.9±4.3%). With time, parallel to the decline in the neointima cellularity, signaling for proliferation and apoptosis decreased. Throughout the time course of neointima development, the apoptotic activity was detected in primarily extravascular cells. Conclusions: Imbalance between proliferation and apoptosis and recruitment of dendritic cells, monocytes/macrophages, and neural crest-derived cells to the injured vessels may partly explain the formation of the hypercellular in-stent neointima. Herein, apoptosis is an important factor that regulates survival of primarily extravascular neointimal cells. [ABSTRACT FROM AUTHOR]

Aims We assessed aortic valves from patients with non-rheumatic aortic valve stenosis (AS) and with degenerative aortic valve bioprostheses (BP) for the presence of progenitor cell and leukocyte subtype-specific markers. [ABSTRACT FROM PUBLISHER]