Smooth muscle phenotypic expression in human carotid arteries. II. Atherosclerosis-free diffuse intimal thickenings compared with the media.

Mosse, Peter R. L.; Campbell, Gordon; Jh, Campbell

doi:10.1161/01.atv.6.6.664

Cited by 123 publications

(101 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…VSMCs displaying the synthetic phenotype are characterized by increased numbers of synthetic organelles such as lysosomes, Golgi, mitochondria, and endoplasmic reticulum, by which proteases are extensively produced. 7,8 These findings and our results suggest that increases in cathepsin D and ACE are associated with the increases in intracellular organelles that occur with the change to the synthetic phenotype and that the increases in cathepsin D and ACE generate Ang II.…”

Section: Discussionsupporting

confidence: 59%

“…After several passages, VSMCs dedifferentiate and display the synthetic phenotype, which is characterized by a reduction in the volume fraction of myofilaments and an increase in synthetic organelles such as the Golgi, mitochondria, and endoplasmic reticulum, by which proteases, growth factors, and cytokines are extensively produced. 7,8 It is possible, therefore, that the mechanism underlying Ang II generation in homogeneous cultures of VSMCs is associated with the change from the contractile to the synthetic phenotype.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Phenotypic Modulation by Fibronectin Enhances the Angiotensin II–Generating System in Cultured Vascular Smooth Muscle Cells

Fukuda

Satoh

et al. 2000

ATVB

View full text Add to dashboard Cite

Abstract-We previously demonstrated that homogeneous cultures of vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats produce angiotensin II (Ang II) in response to increases in the levels of angiotensinogen, cathepsin D, and angiotensin-converting enzyme (ACE). The change of VSMCs from the contractile to the synthetic phenotype increased the amount of synthetic organelles, resulting in the production of proteases and growth factors. To evaluate the contribution of the synthetic phenotype to the generation of Ang II, we examined the effect of fibronectin (FN), which reportedly induces the synthetic phenotype, on the Ang II-generating system in VSMCs. Cultured VSMCs from Wistar-Kyoto rats were incubated with an active fragment of FN, Arg-Gly-Asp-Ser, for 24, 48, or 72 hours after synchronization of the cell cycle with 0.2% calf serum for 48 hours. Immunofluorescence and protein levels of ␣-smooth muscle (SM) actin and expression of SM22␣ mRNA, apparent in the contractile phenotype, were suppressed by FN, whereas expression of matrix Gla mRNA and osteopontin mRNA and protein, apparent in the synthetic phenotype, was increased. FN (1 to 1000 g/mL) dose-dependently increased DNA synthesis in the VSMCs, which was inhibited by the Ang II type 1 receptor antagonist CV-11974. Ang II-like immunoreactivity as determined by radioimmunoassay was significantly increased in conditioned medium from the VSMCs. In addition, mRNA for the Ang II-generating proteases cathepsin D and ACE was increased by FN. Expression of transforming growth factor-␤1, platelet-derived growth factor A-chain, and basic fibroblast growth factor mRNAs was also increased by FN. These results indicate that the changes accompanying the alteration to the synthetic phenotype in homogeneous cultures of VSMCs increase expression of proteases such as cathepsin D and ACE, which then produce Ang II, and that these changes increase expression of growth factors that then induce growth of VSMCs.

show abstract

Section: Discussionsupporting

confidence: 59%

mentioning

confidence: 99%

Phenotypic Modulation by Fibronectin Enhances the Angiotensin II–Generating System in Cultured Vascular Smooth Muscle Cells

Fukuda

Satoh

et al. 2000

ATVB

View full text Add to dashboard Cite

show abstract

“…There was an increase of 318% in the cytoplasmic volume occupied by synthetic organelles of SMCs in areas of DIT, when compared to medial SMCs. Mosse et al (1985), studying human carotids with atherosclerosis, reported a twofold increase in the concentration of organelles of intimal SMCs and a great variability in the content of organelles of these cells when compared to medial SMCs.…”

Section: Discussionmentioning

confidence: 99%

Arterial diffuse intimal thickening associated with enzootic calcinosis of sheep

et al. 1998

View full text Add to dashboard Cite

Pesq. Vet. Bras. 18(1):9-15, jan./mar. 1998 9 RESUMO.-[Espessamento intimal difuso das artérias na calcinose enzoótica dos ovinos.] Foram feitos estudos morfométrico, imunoistoquímico e ultra-estrutural do espessamento intimal difuso (DIT) das artérias de 7 ovinos com sinais clínicos de calcinose enzoótica espontânea causada pela ingestão da planta Nierembergia veitchii. As lesões caracterizavam-se por deposição de sais de cálcio na média como placas e estrias que, com frequência faziam saliência para a luz, criando rugosidades e irregularidades da íntima. Não foram observadas calcificações na artéria pulmonar e no sistema venoso. Microscopicamente, as calcificações das artéri-as restringiam-se quase que exclusivamente à média. Na imunoistoquimica, foi verificada α-actina nas células da mé-dia e nas do espessamento intimal. Receptores para 1,25(OH) 2 D 3 foram evidenciados nos núcleos das células musculares da média, da íntima e das células endoteliais. As aná-lises morfométricas em microscopia ótica revelaram, nas artérias, DIT irregularmente distribuido sem relação com a intensidade dos processos de calcificação subjacente nem com a espessura da média remanescente. A morfometria das alterações ultra-estruturais das células musculares lisas da mé-dia e da íntima espessada, mostrou que nessas últimas foi verificado aumento de até 318% na fração volumétrica das organelas de síntese em detrimento dos elementos contráteis, Morphometric, immunohistochemical and ultrastructural studies were carried out on the diffuse intimal thickening (DIT) in arteries of 7 sheep with clinical signs of naturally occurring enzootic calcinosis due to ingestion of the plant Nierembergia veitchii. Arterial lesions consisted of medial deposition of calcium salts and DIT. Calcification of the intima was rare, mild and located near the elastic lamina. By immunohistochemistry α-actin was detected in cells of the media and in cells forming the intimal thickening. Receptors for 1,25(OH) 2 vitamin D 3 were detected in nuclei of intimal, medial and endothelial cells. DIT was irregularly distributed and was neither proportionally related to the intensity of the underlying mineralization area nor to the thickening of the remaining media. Ultrastructural morphometry in smooth muscle cells (SMCs) of the media and thickened intima revealed, in the latter, an increase of 318% in the volumetric fraction of those organelles involved in synthesis and a proportional decrease in contractile elements when compared to normal values of media cells. There were histological and ultrastructural evidences of modification of SMCs and their migration to the intima, where they proliferated causing DIT. It was concluded that DIT is a consistent component of arteriosclerotic lesions in N. veitchii induced calcinosis of sheep and that the predominant cell in this process is the SMCs originated from its predecessors of the media. It is suggested that the inducing factor for the arterial changes is 1,25(OH) 2 D 3 present in N. veitchii.

show abstract

“…SMCs at the more synthetic end of the phenotype spectrum are assumed to be responsible for ECM synthesis in both the media and intima [25]. Of interest, several studies showed that SMCs located in both intimal thickenings and advanced atherosclerotic lesions display more synthetic features, suggesting that also in atherosclerosis synthetic SMC are responsible for ECM synthesis [25][26][27]. In analogy to the myocardium, the vascular wall also contains fibroblasts, located mainly in the adventitia.…”

Section: S Heeneman Et Almentioning

confidence: 99%

The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis

Heeneman

Cleutjens

Faber

et al. 2003

The Journal of Pathology

120

106

View full text Add to dashboard Cite

The extracellular matrix is no longer seen as the static embedding in which cells reside; it has been shown to be involved in cell proliferation, migration and cell-cell interactions. Turnover of the different extracellular matrix components is an active process with multiple levels of regulation. Collagen, a major extracellular matrix constituent of the myocardium and the arterial vascular wall, is synthesized by (myo)fibroblasts in the myocardium and smooth muscle cells in the medial arterial vascular wall. Its degradation is controlled by proteinases, which include matrix metalloproteinases. This review will focus on the impact of fibrosis and especially collagen turnover on the progression of heart failure and atherosclerosis, two of the main cardiovascular pathologies. We will discuss data from human studies and animal models, with an emphasis on the effects of interventions on collagen synthesis and degradation. We conclude that there is a dynamic (dis)balance in the rate of collagen synthesis and degradation during heart failure and atherosclerosis, which makes the outcome of interventions not always predictable. Alternative approaches for intervening in collagen metabolism will be discussed as possible therapeutic intervention strategies.

show abstract

Smooth muscle phenotypic expression in human carotid arteries. II. Atherosclerosis-free diffuse intimal thickenings compared with the media.

Cited by 123 publications

References 0 publications

Phenotypic Modulation by Fibronectin Enhances the Angiotensin II–Generating System in Cultured Vascular Smooth Muscle Cells

Phenotypic Modulation by Fibronectin Enhances the Angiotensin II–Generating System in Cultured Vascular Smooth Muscle Cells

Arterial diffuse intimal thickening associated with enzootic calcinosis of sheep

The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis

Contact Info

Product

Resources

About