All-trans -retinoic acid decreases cell proliferation and increases apoptosis in an animal model of vein bypass grafting

Leville, Christopher D.; Osipov, Vladimir; Jean-Claude, Jessie; Seabrook, Gary R.; Towne, Jonathan B.; Cambria, Robert A.

doi:10.1067/msy.2000.107371

Cited by 17 publications

(17 citation statements)

References 18 publications

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“…Moreover, RA inhibits the production of several matrix metalloproteinases, and this inhibition may suppress the migration of VSMCs (30,31). Neointima formation after endothelial injury has also been shown to be inhibited by RA treatment in vivo (27,32,33). Taken together, these results indicate that retinoids exert anti-atherosclerotic effects in VSMCs.…”

Section: Discussionsupporting

confidence: 61%

“…Retinoids downregulate angiotensin II (AII) type 1 receptor expression in VSMCs, resulting in the inhibition of AII actions on VSMCs (24,25). Retinoids have also been reported to induce apoptosis in VSMCs (26,27). Incubation of multipotential P19 embryonal carcinoma cells with retinoids induces differentiation of VSMCs through the induction of α-smooth muscle actin (28,29).…”

Section: Discussionmentioning

confidence: 99%

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Transcription Suppression of Thromboxane Receptor Gene Expression by Retinoids in Vascular Smooth Muscle Cells

et al. 2003

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Transcription Suppression of Thromboxane Receptor Gene Expression by Retinoids in Vascular Smooth Muscle Cells

et al. 2003

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“…1 It has recently been shown that atRA treatment may be beneficial in models of cardiovascular disease [2][3][4][5][6][7][8]22,23 although the mechanisms involved are not understood. The present study demonstrates that atRA increases nitrite production by endothelial cells in a time-dependent manner and suggests that the upregulation of the enzyme DDAH II in endothelial cells contributes to this effect.…”

Section: Discussionmentioning

confidence: 99%

“…atRA regulates angiogenesis, 1 may retard the development of atherosclerosis, 2 inhibits neointima formation, and alters remodeling after vascular injury or bypass grafting. [3][4][5][6][7] The mechanisms involved are poorly understood and attention has previously focused on vascular smooth muscle cell (VSMC) effects. 8 However, there are good reasons to suspect that atRA may also affect the endothelium.…”

mentioning

confidence: 99%

all- trans -Retinoic Acid Increases Nitric Oxide Synthesis by Endothelial Cells

Achan

Tran

Arrigoni

et al. 2002

Circulation Research

128

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Abstract-all-trans-Retinoic acid (atRA) has important effects on the developing and mature cardiovascular system. Nitric oxide (NO) production has been associated with the atRA-induced differentiation of neuronal cells, and we hypothesized that NO may also mediate certain actions of atRA in the cardiovascular system. We studied the effects of atRA on NO production by endothelial cells and determined whether regulation of enzymes responsible for metabolism of asymmetric dimethylarginine (ADMA) contributed to the effects seen. Murine endothelioma (sEnd.1) cells were incubated with or without atRA. Nitrite production was determined using the Griess reaction. The expression of NO synthase (NOS) and dimethylarginine dimethylaminohydrolase (DDAH) genes was determined by Northern blotting. A reporter gene assay was also used to study the effect of atRA on the DDAH II promoter. atRA significantly increased nitrite production by sEnd.1 cells despite no increase in eNOS expression. atRA also increased DDAH II gene expression and promoter activity and reduced the ratio of ADMA to symmetric dimethylarginine (SDMA) in culture medium. The DDAH inhibitor 4124W significantly reduced the induction of NO synthesis by atRA. The present study demonstrates that atRA increases NO synthesis in endothelial cells without increasing eNOS expression. atRA also increases the expression of DDAH II, the predominant DDAH isoform in endothelial cells. Our data suggests that the induction of NO synthesis by atRA may be facilitated by DDAH II. This pathway may help to explain some of the effects of atRA on the cardiovascular system. Key Words: asymmetric methylarginine Ⅲ dimethylarginine dimethylaminohydrolase Ⅲ endothelium Ⅲ nitric oxide Ⅲ retinoic acid V itamin A derivatives (retinoids), and in particular alltrans-retinoic acid (atRA), inhibit cellular proliferation and promote cellular differentiation. These actions have important effects on the developing as well as the mature cardiovascular system and have potential therapeutic value. atRA regulates angiogenesis, 1 may retard the development of atherosclerosis, 2 inhibits neointima formation, and alters remodeling after vascular injury or bypass grafting. [3][4][5][6][7] The mechanisms involved are poorly understood and attention has previously focused on vascular smooth muscle cell (VSMC) effects. 8 However, there are good reasons to suspect that atRA may also affect the endothelium. Endothelial cells are exposed to the highest concentration of circulating atRA, express retinoid receptors, and play a significant role in atRA metabolism compared with other cell types. 9 atRA also modulates endothelial cell growth, differentiation, and morphology. 10,11 Recent data suggests that the effects of retinol (vitamin A alcohol) on VSMC function may depend on an unknown endothelial factor. 12 NO released by endothelial cells is an important regulator of vascular function. The cellular effects of NO bear some similarity to those of atRA, and NO has been implicated in the atRA-induced differentiation ...

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“…6 Experimental models that mimic clinical vein grafting show a characteristic burst of neointimal cell proliferation early after grafting (3 to 7 days), which leads to a thickened intimal layer by 1 month. 7,8 This neointimal growth appears to stabilize beyond 1 to 2 months in animal models 9,10 and does not create significant graft stenosis at any time, thus differing from the clinical progression of this complication. …”

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confidence: 99%

Murine Model of Neointimal Formation and Stenosis in Vein Grafts

Cooley

2004

ATVB

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Objective-Previous studies have suggested that neointimal formation, a central cause of vein graft stenosis, has several potential cell sources. It was hypothesized that neointimal cells arise primarily from the cells of the vein graft. Methods and Results-This study investigated vein graft neointimal cell origins using a model of vein-to-artery cross-transplantation between transgenic Rosa26 mice (constitutive expression of bacterial ␤-galactosidase marker gene) and wild-type mice. Vein-originating cells survived and make a major contribution to neointimal formation within the vein graft, mostly adjacent to the lumen/endothelium, suggesting an intimate association with endothelial cells. Key Words: bypass graft Ⅲ neointima Ⅲ Rosa26 Ⅲ thrombomodulin Ⅲ stenosis V ascular bypass surgery using vein grafts has become an established procedure for treating many conditions, most notably myocardial infarction (eg, coronary bypass) and limb claudication (eg, femoral-popliteal bypass grafting). 1,2 Despite high early success rates of these procedures, it is estimated that 20% to 50% of cases undergo stenotic occlusion of the graft within 5 years, 3-5 caused by an inward growth of neointimal cells. 6 Experimental models that mimic clinical vein grafting show a characteristic burst of neointimal cell proliferation early after grafting (3 to 7 days), which leads to a thickened intimal layer by 1 month. 7,8 This neointimal growth appears to stabilize beyond 1 to 2 months in animal models 9,10 and does not create significant graft stenosis at any time, thus differing from the clinical progression of this complication. See page 1147The source of neointimal cells remains controversial. Studies using arterial injury models (eg, balloon angioplasty) have presented evidence for medial smooth muscle cells, adventitial (myo)fibroblasts, and blood-borne stem cells as major contributors to the neointima. 11-15 Studies using vein graft models have supported adjacent arterial media as a major source for neointimal cells. 7,16 Arterial and organ allotransplantation models have found that circulating progenitor cells and adjacent (recipient) arterial media are the major contributors to transplant-associated neointimal formation. 15,[17][18][19] A recent study using a murine vein graft model demonstrated that the neointimal cells within the graft arise from both the vein graft and the recipient artery. 20 The following study confirms this result using a new murine model that has direct analogy to clinical vein grafting and stenosis. Furthermore, the findings show that neointima cells from the vein graft arise from and proliferate predominantly at the innermost (luminal) aspect, suggesting involvement of vein-derived endothelial cells. Methods Vein Graft ModelA new model of vein graft transplantation in mice was developed by the author and is similar to recently described murine vein graft models 20 -22 but uses a smaller-diameter graft, a branch of the jugular vein, interpositioned to the femoral artery. This model has more clinical analogy...

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All-trans -retinoic acid decreases cell proliferation and increases apoptosis in an animal model of vein bypass grafting

Cited by 17 publications

References 18 publications

Transcription Suppression of Thromboxane Receptor Gene Expression by Retinoids in Vascular Smooth Muscle Cells

Transcription Suppression of Thromboxane Receptor Gene Expression by Retinoids in Vascular Smooth Muscle Cells

all- trans -Retinoic Acid Increases Nitric Oxide Synthesis by Endothelial Cells

Murine Model of Neointimal Formation and Stenosis in Vein Grafts

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