Topographic Analysis of Proliferative Activity in Carotid Endarterectomy Specimens by Immunocytochemical Detection of the Cell Cycle–Related Antigen Ki-67

Brandl, Richard; Richter, Thomas; Haug, K.; Wilhelm, Manfred; Maurer, P.; Nathrath, W

doi:10.1161/01.cir.96.10.3360

Cited by 48 publications

(46 citation statements)

References 39 publications

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“…In contrast, the saturated acyl species are inactive in eliciting vascular wall remodeling [43,55]. Using atherosclerotic tissue specimens from patients who underwent operations for high-grade carotid stenosis, we analyzed the LPA content and composition of the lipid-rich core that is characterized histologically by extracellular lipid deposits and beds of foam cells [80]. This region had the highest LPA content [77,81].…”

Section: Discussionmentioning

confidence: 99%

The early- and late stages in phenotypic modulation of vascular smooth muscle cells: Differential roles for lysophosphatidic acid

Guo

Makarova

Cheng

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Lysophosphatidic acid (LPA) has been implicated as causative in phenotypic modulation (PM) of cultured vascular smooth muscle cells (VSMC) in their transition to the dedifferentiated phenotype. We evaluated the contribution of the three major LPA receptors, LPA 1 and LPA 2 GPCR and PPARγ, on PM of VSMC. Expression of differentiated VSMC-specific marker genes, including smooth muscle α-actin, smooth muscle myosin heavy chain, calponin, SM-22α, and hcaldesmon, was measured by quantitative real-time PCR in VSMC cultures and aortic rings kept in serum-free chemically defined medium or serum-or LPA-containing medium using wild-type C57BL/6, LPA 1 , LPA 2 , and LPA 1&2 receptor knockout mice. Within hours after cells were deprived of physiological cues, the expression of VSMC marker genes, regardless of genotype, rapidly decreased. This early PM was neither prevented by IGF-I, inhibitors of p38, ERK1/2, or PPARγ nor significantly accelerated by LPA or serum. To elucidate the mechanism of PM in vivo, carotid artery ligation with/without replacement of blood with Krebs solution was used to evaluate contributions of blood flow and pressure. Early PM in the common carotid was induced by depressurization regardless of the presence/absence of blood, but eliminating blood flow while maintaining blood pressure or after sham surgery elicited no early PM. The present results indicate that LPA, serum, dissociation of VSMC, IGF-I, p38, ERK1/2, LPA 1 , and LPA 2 are not causative factors of early PM of VSMC. Tensile stress generated by blood pressure may be the fundamental signal maintaining the fully differentiated phenotype of VSMC.

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Section: Discussionmentioning

confidence: 99%

The early- and late stages in phenotypic modulation of vascular smooth muscle cells: Differential roles for lysophosphatidic acid

Guo

Makarova

Cheng

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…The majority of data on DNA synthesis in human atherosclerosis are confined to advanced lesions only. They show low levels of DNA synthesis (0% to 2%), [15][16][17][18] but this level is significantly higher than in the nondiseased arterial wall. 14,15,18,19 One study on DNA synthesis in early fatty-streak lesions also reports low values of DNA synthesis (0% to 2%).…”

Section: Discussionmentioning

confidence: 99%

“…They show low levels of DNA synthesis (0% to 2%), [15][16][17][18] but this level is significantly higher than in the nondiseased arterial wall. 14,15,18,19 One study on DNA synthesis in early fatty-streak lesions also reports low values of DNA synthesis (0% to 2%). 20 DNA synthesis in these human lesions is confined primarily to either the macrophage-derived foam cell 15,17,18 or the VSMC.…”

Section: Discussionmentioning

confidence: 99%

“…14,15,18,19 One study on DNA synthesis in early fatty-streak lesions also reports low values of DNA synthesis (0% to 2%). 20 DNA synthesis in these human lesions is confined primarily to either the macrophage-derived foam cell 15,17,18 or the VSMC. 16 As in human in vitro studies 21 and rabbit models, [22][23][24] the APOE*3-Leiden mouse exhibits a DNAsynthesis peak in early lesion types.…”

Section: Discussionmentioning

confidence: 99%

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Atherosclerosis in APOE*3-Leiden Transgenic Mice

et al. 1999

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Background-This study documents (1) the progression of atherosclerosis along the entire arterial tree in APOE*3-Leiden mice after 1, 4, 6, 9, and 12 months of a high-fat/high-cholesterol (HFC) diet and (2) the amount and phenotype of DNA-synthesizing and apoptotic cells in different lesion types after 6 months of HFC diet. Methods and Results-Diet duration was correlated with a craniocaudal progression of lesion development and with an increase in severity of the lesion. Typically, the lesions contained smooth muscle cells, macrophages, and T lymphocytes and were covered by an intact endothelium. Whereas DNA synthesis (BrdU uptake) was usually elevated in type II lesions (8.6Ϯ0.8% versus 1.0Ϯ0.2% in the nondiseased arterial wall; PϽ0.05), apoptosis was found primarily in advanced lesions (type IV, 1.3Ϯ0.1% and type V, 1.2Ϯ0.2% versus 0.04Ϯ0.04% in the nondiseased arterial wall [PϽ0.05]). Cell phenotyping revealed that the majority of DNA synthesis and apoptosis was confined to the macrophage-derived foam cell (68.6Ϯ3.0% and 82.2Ϯ4.6%, respectively). Conclusions-This study shows that in APOE*3-Leiden mice, duration of an HFC diet is associated with (1) a craniocaudal progression of lesion development and (2) an increased complexity of atherosclerotic lesions. Furthermore, DNA synthesis is predominant in early lesions, whereas apoptosis is present mainly in more advanced lesions. Both parameters of cell turnover are confined primarily to the macrophage-derived foam cell. (Circulation. 1999;99:276-283.)

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“…It may also be argued that apoptotic death of any cell type in the plaque may favour plaque regression over plaque progression. However, the rate of apoptotic cell death in the plaque (2 ± 10%) (Bauriedel et al, 1998;Kockx et al, 1996;Mallat et al, 1997) may, in many instances, exceed the reported rate of cell proliferation (51%) (Brandl et al, 1997;Gordon et al, 1990). In the light of observations that human atherosclerotic plaques are generally more prone to progression rather than regression, it can be suggested that apoptosis is actually implicated in natural plaque progression (rather than regresssion), through development of the acellular lipid necrotic' core.…”

Section: Apoptosis In the Vasculaturementioning

confidence: 97%

Apoptosis in the vasculature: mechanisms and functional importance

Mallat¹,

Tedgui²

2000

British J Pharmacology

307

214

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Apoptotic death has now been recognized in a number of common and threatening vascular diseases, including atherosclerosis. Interest in apoptosis research relates to the fact that apoptosis, in contrast to oncosis, is a highly regulated process of cell death which raises the hope for the development of speci®c therapeutic strategies to alter disease progression. This review summarizes the mechanisms involved in vascular endothelial and smooth muscle cell survival/apoptosis, and the potential roles of apoptotic death in atherosclerosis and restenosis. The potential e ects of modulation of apoptosis in these diseases are also discussed.

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Topographic Analysis of Proliferative Activity in Carotid Endarterectomy Specimens by Immunocytochemical Detection of the Cell Cycle–Related Antigen Ki-67

Cited by 48 publications

References 39 publications

The early- and late stages in phenotypic modulation of vascular smooth muscle cells: Differential roles for lysophosphatidic acid

The early- and late stages in phenotypic modulation of vascular smooth muscle cells: Differential roles for lysophosphatidic acid

Atherosclerosis in APOE*3-Leiden Transgenic Mice

Apoptosis in the vasculature: mechanisms and functional importance

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