INTIMAL LAMINATED ELASTOSIS IN THE INTRARENAL ARTERIES An Electron Microscopic Study

Kojimahara, Masayasu

doi:10.1111/j.1440-1827.1988.tb02304.x

Cited by 4 publications

(5 citation statements)

References 14 publications

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“…24 In some regions, the elastin was less organized and was arranged as bundles of fibers (Figure 7f) similar to that seen for vector-alone neointima (Figure 7e). The total volume fraction of elastin, determined by point counting from electron micrographs, was significantly higher in neointima formed by V3-transduced cells (Figure 8).…”

Section: Merrilees Et Alsupporting

confidence: 60%

Retrovirally Mediated Overexpression of Versican V3 by Arterial Smooth Muscle Cells Induces Tropoelastin Synthesis and Elastic Fiber Formation In Vitro and In Neointima After Vascular Injury

Merrilees

Lemire

Fischer

et al. 2002

Circulation Research

100

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Abstract-Versican is an extracellular matrix (ECM) proteoglycan that is synthesized as multiple splice variants. In a recent study, we demonstrated that retroviral-mediated overexpression of the variant V3, which lacks chondroitin sulfate (CS) chains, altered arterial smooth muscle cell (ASMC) phenotype in short-term cell culture. We now report that V3-overexpressing ASMCs exhibit significantly increased expression of tropoelastin and increased formation of elastic fibers in long-term cell cultures. In addition, V3-overexpressing ASMCs seeded into ballooned rat carotid arteries continued to overexpress V3 and, at 4 weeks after seeding, produced a highly structured neointima significantly enriched in elastic fiber lamellae. In contrast to the hydrated, myxoid neointima produced by rounded or stellate vector-alonetransduced cells, V3-expressing cells produced a compact and highly ordered neointima, which contained elongated ASMCs that were arranged in parallel arrays and separated by densely packed collagen bundles and elastic fibers. These results indicate that a variant of versican is involved in elastic fiber assembly and may represent a novel therapeutic approach to facilitate the formation of elastic fibers. T he extracellular matrix (ECM) proteoglycan versican, the major chondroitin sulfate proteoglycan of vessel wall, 1 is distinguished by a central extended region with attached glycosaminoglycan (GAG) chains by an amino-terminal globular domain (G1) that binds hyaluronan (HA) and by a carboxy-terminal selectin-like domain (G3) that binds to other matrix components including tenascin-R and fibulin-1. [2][3][4][5][6] The mRNA that codes the GAG attachment region, which in the full-length form has 2 domains, can undergo differential splicing to produce 4 variants: V0, with 2 (␣ and ␤) GAG binding regions; V1 (with the ␤ GAG exon); V2 (with the ␣ GAG exon); and V3 with neither GAG exon and formed from the G1 and G3 domains only. 7-9 V3 is thus predicted to be a glycoprotein and not a proteoglycan. V3 mRNA has been demonstrated in aortic tissue as well as cultures of ASMCs by Northern blot 10 and has been detected, by polymerase chain reaction (PCR), from cDNA libraries for various tissues including brain, stomach, and liver. 9 Recently, we reported that retroviral insertion and overexpression of the gene for V3 into cultured Fischer rat ASMCs induces a number of phenotypic changes. 11 Compared with vector-alone-transduced cells, V3 ASMCs are more flattened and spread, show a large increase in area of close contacts and in the size of peripheral focal contacts, increased resistance to trypsin detachment, reduced pericellular coats, and decreased rates of growth and migration. The mechanism by which V3 effects these changes is not clear, although the morphological features, the reduced growth and migration, and the reduced cell coat, raise the possibility that V3 may affect the accumulation of components of the extracellular matrix. For example, Evanko et al 12 showed recently that the V1 isoform of versican in ...

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Section: Merrilees Et Alsupporting

confidence: 60%

Retrovirally Mediated Overexpression of Versican V3 by Arterial Smooth Muscle Cells Induces Tropoelastin Synthesis and Elastic Fiber Formation In Vitro and In Neointima After Vascular Injury

Merrilees

Lemire

Fischer

et al. 2002

Circulation Research

100

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“…The bands of elastin between adjacent ASMC were frequently bilamina (Figure 3F and 3G), indicative of a dual origin from opposing parallel ASMC, a feature reported previously for formation of medial elastic lamellae. 32 …”

Section: Resultsmentioning

confidence: 99%

Neointima Formed by Arterial Smooth Muscle Cells Expressing Versican Variant V3 Is Resistant to Lipid and Macrophage Accumulation

Merrilees

Beaumont

Braun

et al. 2011

ATVB

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Objective Extracellular matrix (ECM) of neointima formed following angioplasty contains elevated levels of versican, loosely arranged collagen, and fragmented deposits of elastin, features associated with lipid and macrophage accumulation. ECM with a low versican content, compact structure and increased elastic fiber content can be achieved by expression of versican variant V3, which lacks chondroitin sufate (CS) glycosaminoglycans (GAG). We hypothesized that V3-expressing arterial smooth muscle cells (ASMC) can be utilized to form a neointima resistant to lipid and macrophage accumulation associated with hypercholesterolemia. Methods and Results ASMC transduced with V3 cDNA were seeded into ballooned rabbit carotid arteries and animals fed a chow diet for four weeks, followed by a cholesterol-enriched diet for four weeks, achieving plasma cholesterol levels of 20–25mmol/L. V3 neointimae at eight weeks were compact, multilayered and elastin-enriched. They were significantly thinner (57%) than control neointimae, contained significantly more elastin (118%), less collagen (22%) and less lipid (76%), and showed significantly reduced macrophage infiltration (85%). Mechanistic studies demonstrated that oxidized LDL stimulated the formation of this monocyte binding ECM which was inhibited in the presence of V3 expressing ASMC. Conclusion These results demonstrate that expression of V3 in vessel wall creates an elastin-rich neointimal matrix that in the presence of hyperlipidemia is resistant to lipid deposition and macrophage accumulation.

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“…The turnover of vascular elastin is very slow, with a half-life of 60-70 years, which means that structurally functional vascular elastin is primarily produced during childhood (21). Upon degradation of elastin in IA, SMCs (22) and macrophages (23) deposit intimal elastic tissue. Although this intimal elastic tissue consists of elastin, its functional properties are lost (20).…”

Section: Internal Elastic Laminamentioning

confidence: 99%

“…Clear increase in the intimal elastic tissue deposition in the ruptured IA suggests that further structural remodeling is activated before the rupture. The thickened IEL with presence of intimal elastic tissue and inherent loss of elastic function leads to increase in wall stiffness and decreases distensibility and contributes to susceptibility to hemodynamic factors (21)(22)(23)(24). This in combination with increased inflammation might make the lesions more prone to rupture.…”

Section: Internal Elastic Laminamentioning

confidence: 99%

Comparative Ultrastructural and Stereological Analyses of Unruptured and Ruptured Saccular Intracranial Aneurysms

Korkmaz

Kleinloog

Verweij

et al. 2017

Journal of Neuropathology &Amp; Experimental Neurology

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Insight into processes leading to rupture of intracranial aneurysms (IAs) may identify biomarkers for rupture or lead to management strategies reducing the risk of rupture. We characterized and quantified (ultra)structural differences between unruptured and ruptured aneurysmal walls. Six unruptured and 6 ruptured IA fundi were resected after microsurgical clipping and analyzed by correlative light microscopy for quantitative analysis (proportion of the vessel wall area) and transmission electron microscopy for qualitative ultrastructural analysis. Quantitative analysis revealed extensive internal elastic lamina (IEL) thickening in ruptured IA (36.3% ± 15%), while thin and fragmented IEL were common in unruptured IA (5.6% ± 7.1%). Macrophages were increased in ruptured IA (28.3 ± 24%) versus unruptured IA (2.7% ± 5.5%), as were leukocytes (12.85% ± 10% vs 0%). Vasa vasorum in ruptured but not in unruptured IA contained vast numbers of inflammatory cells and extravasation of these cells into the vessel wall. In conclusion, detection of thickened IEL, leaky vasa vasorum, and heavy inflammation as seen in ruptured IA in comparison to unruptured IA may identify aneurysms at risk of rupture, and management strategies preventing development of vasa vasorum or inflammation may reduce the risk of aneurysmal rupture.

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INTIMAL LAMINATED ELASTOSIS IN THE INTRARENAL ARTERIES An Electron Microscopic Study

Cited by 4 publications

References 14 publications

Retrovirally Mediated Overexpression of Versican V3 by Arterial Smooth Muscle Cells Induces Tropoelastin Synthesis and Elastic Fiber Formation In Vitro and In Neointima After Vascular Injury

Retrovirally Mediated Overexpression of Versican V3 by Arterial Smooth Muscle Cells Induces Tropoelastin Synthesis and Elastic Fiber Formation In Vitro and In Neointima After Vascular Injury

Neointima Formed by Arterial Smooth Muscle Cells Expressing Versican Variant V3 Is Resistant to Lipid and Macrophage Accumulation

Comparative Ultrastructural and Stereological Analyses of Unruptured and Ruptured Saccular Intracranial Aneurysms

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