Sphingosine-1-Phosphate Receptor 3 Promotes Neointimal Hyperplasia in Mouse Iliac-Femoral Arteries

Shimizu, Takuya; Wispelaere, Allison De; Winkler, Martin Sebastian; D'Souza, Travis; Caylor, Jacob; Chen, Lihua; Dastvan, Frank; Deou, Jessie; Cho, Aesim; Larena-Avellaneda, A.; Reidy, Michael A.; Daum, Guenter

doi:10.1161/atvbaha.111.241034

Cited by 20 publications

(11 citation statements)

References 41 publications

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“…The exposed muscular branch artery was dilated by topical application of one drop of 1 % lidocaine hydrochloride. The injury model of the femoral artery was performed as described [31] with some modifications. Briefly, the end-blunted 31-gauge needle (0.26 mm in diameter) was inserted into the profunda femoris artery, pushed forward for ∼5–10 mm toward the iliac artery and left in place for 1 min, to dilate the artery.…”

Section: Methodsmentioning

confidence: 99%

Smooth muscle cells from the anastomosed artery are the major precursors for neointima formation in both artery and vein grafts

Liang

Wang

et al. 2014

Basic Res Cardiol

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Accumulation of smooth muscle cells (SMC) results in neointima formation in injured vessels. Two graft models consisting of vein and artery grafts were created by anastomosing common carotid arteries to donor vessels. To identify the origin of the neointima cells from anastomosed arteries, we use Wnt1-Cre/reporter mice to label and track SMCs in the common carotid artery. The contribution of SMCs in the neighboring arteries to neointima formation was studied. On evaluating the artery grafts after 1 month, >90 % of the labeled neointima cells were found to have originated from the anastomosing host arteries. Most of the neointima cells were also smooth muscle α-actin positive (SMA-α+) and expressed the smooth muscle myosin heavy chain (SMMHC), the SMC terminal differentiation marker. In vein grafts, about 60 % SMA-α-positive cells were from anastomosing arteries. Bone marrow cells did not contribute to neointima SMCs in vein grafts, but did co-stain with markers of inflammatory cells. Wnt1 expression was not detected in the neointima cells in the vein or artery grafts, or the injured femoral arteries. Neointima SMCs showed the synthetic phenotype and were positively labeled with BrdU in vitro and in vivo. Treatment with the IGF-1 receptor inhibitor suppressed SMC proliferation and neointima formation in vein grafts. Our results indicate that SMCs from the neighboring artery are predominantly present in the neointima formed in both vein and artery grafts and that Wnt1-Cre mice can be used to explore the role of SMCs originating from neighboring vessels in vascular remodeling.

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Section: Methodsmentioning

confidence: 99%

Smooth muscle cells from the anastomosed artery are the major precursors for neointima formation in both artery and vein grafts

Liang

Wang

et al. 2014

Basic Res Cardiol

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“…This receptor seems to share some properties with S1P1 and other with S1P2. S1P3 is expressed in various cell types and can regulate cell migration, proliferation and survival through a Gi/Gq-dependent activation of PLC/PI3K/Akt [218] . It also regulates the contraction of vascular SMCs through a calcium-dependent mechanism [212] .…”

Section: Mechanisms Of Plaque Neovascularizationmentioning

confidence: 99%

Angiogenesis in the atherosclerotic plaque

et al. 2017

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Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations.

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“…Evidence from studies using genetic and pharmacologic approaches to target specific LPA and S1P receptors, supports their role in regulating neointimal growth in response to vascular injury in mice. The development of intimal hyperplasia likely results from effects of LPA or S1P on multiple cell types, including recruitment of inflammatory and progenitor cells and stimulation of resident SMC 4, 20–25 . Moreover, LPA heightens atherosclerotic plaque burden in apolipoprotein E-deficient ( Apoe −/−) mice in an LPA 1 - and LPA 3 -dependent manner 26 .…”

mentioning

confidence: 99%

Lipid Phosphate Phosphatase 3 Negatively Regulates Smooth Muscle Cell Phenotypic Modulation to Limit Intimal Hyperplasia

Panchatcharam

Miriyala

Salous

et al. 2013

ATVB

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Rationale The lipid phosphate phosphatase 3 (LPP3) degrades bioactive lysophospholipids including lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) and thereby terminates their signaling effects. While emerging evidence links LPA to atherosclerosis and vascular injury responses, little is known about the role of vascular LPP3. Objective The goal of this study was to determine the role of LPP3 in the development of vascular neointima formation and smooth muscle cells (SMC) responses. Methods and Results We report that LPP3 is expressed in vascular SMC following experimental arterial injury. Using gain- and loss-of-function approaches, we establish that a major function of LPP3 in isolated SMC cells is to attenuate proliferation, (ERK) activity, Rho activation, and migration in response to serum and LPA. These effects are at least partially a consequence of LPP3-catalyzed LPA hydrolysis. Mice with selective inactivation of LPP3 in SMC display an exaggerated neointimal response to injury. Conclusions Our observations suggest that LPP3 serves as an intrinsic negative regulator of SMC phenotypic modulation and inflammation after vascular injury, in part by regulating lysophospholipid signaling. These findings may provide a mechanistic link to explain the association between a PPAP2B polymorphism and coronary artery disease risk.

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Sphingosine-1-Phosphate Receptor 3 Promotes Neointimal Hyperplasia in Mouse Iliac-Femoral Arteries

Cited by 20 publications

References 41 publications

Smooth muscle cells from the anastomosed artery are the major precursors for neointima formation in both artery and vein grafts

Smooth muscle cells from the anastomosed artery are the major precursors for neointima formation in both artery and vein grafts

Angiogenesis in the atherosclerotic plaque

Lipid Phosphate Phosphatase 3 Negatively Regulates Smooth Muscle Cell Phenotypic Modulation to Limit Intimal Hyperplasia

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