Arterial Wall Cell Proliferation Research Articles

High glucose promotes vascular smooth muscle cell proliferation by upregulating proto-oncogene serine/threonine-protein kinase Pim-1 expression.

Serine/threonine kinase proviral integration site for Moloney murine leukemia virus 1 (Pim-1) plays an essential role in arterial wall cell proliferation and associated vascular diseases, including pulmonary arterial hypertension and aortic wall neointima formation. Here we tested a role of Pim-1 in high-glucose (HG)-mediated vascular smooth muscle cell (VSMC) proliferation. Pim-1 and proliferating cell nuclear antigen (PCNA) expression levels in arterial samples from streptozotocin-induced hyperglycemia rats were increased, compared with their weak expression in normoglycemic groups. In cultured rat VSMCs, HG led to transient Pim-1 expression decline, followed by sustained expression increase at both transcriptional and translational levels. Immunoblot analysis demonstrated that HG increased the expression of the 33-kDa isoform of Pim-1, but at much less extent to its 44-kDa plasma membrane isoform. D-glucose at a concentration of 25 mmol/L showed highest activity in stimulating Pim-1 expression. Both Pim-1 inhibitor quercetagetin and STAT3 inhibitor stattic significantly attenuated HG-induced VSMC proliferation and arrested cell cycle progression at the G1 phase. Quercetagetin showed no effect on Pim-1 expression but decreased the phosphorylated-Bad (T112)/Bad ratio in HG-treated VSMCs. However, stattic decreased phosphorylated-STAT3 (Y705) levels and caused transcriptional and translational down-regulation of Pim-1 in HG-treated VSMCs. Our findings suggest HG-mediated Pim-1 expression contributes to VSMC proliferation, which may be partly due to the activation of STAT3/Pim-1 signaling.

Chronological Changes in Morphometry and Histology in the Rabbit Vascular Wall after External Radiation for the Prevention of Intimal Hyperplasia

Although ionizing radiation has been proposed for the prevention of intimal hyperplasia in coronary and peripheral arteries, information is lacking on how irradiation affects arterial histology and neointimal smooth-muscle cell proliferation-the hallmark of restenosis. We chronologically investigated early histological changes and quantitative changes in arterial wall cell proliferation after arterial injury followed by external radiation for the prevention of intimal hyperplasia in rabbits. The aorta was experimentally injured in 26 rabbits who were then assigned to two groups: irradiation with 20 Gy and a control group with no irradiation. The aorta was resected for morphometric and histological studies at 3, 7, 15, 30, and 45 days after experimental injury. Intimal thickness was reduced and the intima/media ratio was significantly lower in irradiated groups than in control rabbits. In the irradiated group histological examination showed delayed neointimal proliferation with an intact endothelium. In the 20-Gy irradiated group the vascular media at 7 days contained necrotic areas and delayed fibrosis with calcifications. There was no statistical difference between the number of proliferating cells in the irradiated groups and the control group. Proliferating cells reached maximum numbers later in irradiated groups than in control rabbits (45 days versus 3 days). After arterial injury, external irradiation at 20 Gy effectively reduced aortic neointimal thickening. Irradiation-induced histological changes include recasting with rapid necrosis and delayed fibrosis. Radiation-induced parietal recasting with necrosis, fibrosis, and calcifications might worsen in time. Although irradiation after arterial injury leaves proliferative smooth-muscle cells within the arterial wall quantitatively unchanged in the early days after the procedure, it then induces a delayed reaction (observed over 45 days in our study). Whether neointimal hyperplasia is merely delayed or will ultimately develop causing restenosis awaits confirmation from experimental and clinical studies with a long-term follow-up.

Parenchymal cell proliferation in coronary arteries after percutaneous transluminal coronary angioplasty: a human tissue bank study

Purpose: Restenosis after percutaneous transluminal coronary angioplasty (PTCA) remains a limitation of this technique. Arterial wall cell proliferation is a component of restenosis preventable with intravascular brachytherapy. This study attempts to locate the sites of cellular proliferation after PTCA so as to aid the optimization of this therapy. Methods and Materials: Autopsy records from January 1, 1985 through December 31, 1995 were reviewed, and 27 patients who received PTCA prior to death were identified who also had evidence of PTCA on histologic examination of the arterial sections. The sections were subjected to immunohistochemical staining for proliferating cell nuclear antigen (PCNA) to detect the proliferating cells in the arterial sections, followed by image analysis to determine the proliferative index (PI) of all regions and layers of the section. Results: The PI did not differ significantly according to vessel region (plaque, plaque shoulder, or portion of vessel wall with lowest plaque burden), vessel layer (intima, media, adventitia), or evidence of prior PTCA. There was a trend toward a higher PI in young lesions. Conclusion: Cell proliferation in the vascular wall after PTCA was found throughout the treated arterial section’s axial plane, not only in the periluminal region.

About the effect of risk factors on the structure and the proliferation of arterial wall cells: Part 1: Changes in structure and proliferation of cultivated aortic smooth muscle cells from hypertensive-diabetic rats

In cultivated aortic smooth muscle cells (SMC) from normal or hypertensive-diabetic rats respectively, two types of cells, small SMC and large ones, were observed. The differences between the surface areas, form factors and nucleus-plasma relations of the small and the large cells, measured by morphometric methods are evident. The ratio of small to large cells originating from the normal group was 87%: 13%, and of those originating from the hypertensive-diabetic group 76%: 24%. The percentages of polynuclear cells from the normal group were 3.9% and from the hypertensive-diabetic group 6.1%. The small cells from hypertensive-diabetic rats proliferated faster (3H-thymidine labeling index 23.7%) than those from the control rats (3H-thymidine labeling index 12.9%). Their large cells showed on the contrary a trend to slower proliferation.

About the effect of risk factors on the structure and the proliferation of arterial wall cells: Part 2: Changes in structure and proliferation of cultivated aortic endothelial cells from hypertensive minipigs

Cultured aortic endothelial cells (EC) from normotensive and hypertensive minipigs were studied in the second passage. Cytological measurements performed on confluent cultures of the same age in the second subculture revealed significant smaller surface areas and circumferences of EC and of their nuclei in the hypertensive group compared to those in the normotensive control group. The percentage of polynuclear EC was higher in cultures from hypertensive animals than in cultures from normotensive ones. EC derived from hypertensive minipigs differed from those of normotensive animals by a higher rate of proliferation as shown by 3H-thymidine labeling of the cells and by comparison of growth curves.