Bone morphogenetic protein 4: Potential regulator of shear stress-induced graft neointimal atrophy

Hsieh, Patrick C.H.; Kenagy, Richard D.; Mulvihill, Eileen R.; Jeanette, Joseph P.; Wang, Xi; Chang, Cindy M.; Yao, Zizhen; Ruzzo, Walter L.; Justice, Suzanne; Hudkins, Kelly L.; Alpers, Charles E.; Berceli, Scott A.; Clowes, Alexander W.

doi:10.1016/j.jvs.2005.08.008

Cited by 23 publications

(27 citation statements)

References 62 publications

(82 reference statements)

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“…BMP4 mRNA expression was slightly increased by day 1 but significantly increased at 7 days compared to normal flow grafts [13]. We observed a similar time course of Bmp4-lacZ induction in ligated mouse carotid arteries.…”

Section: Discussionsupporting

confidence: 74%

“…For example, Wong failed to demonstrate an effect of rhBMP2 on a human aortic SMC apoptosis after 24 hours [28], while Zhang et al observed increased apoptosis in pulmonary artery SMCs harvested from patients with primary pulmonary hypertension and treated with rhBMP2 for 48 hours [32]. Increased SMC apoptosis has recently been demonstrated in baboon neointimal cells exposed to rhBMP4 but only after 48 and 72 hours [13]. It is also possible that the effects of BMPs on SMC apoptosis are transduced through other signaling mechanisms that do not involve Alk-3.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, cultured endothelial cells have been shown to express BMP4 in response to both cytokines and oscillatory shear stress [12]. Additionally, flow alterations in PTFE arterial grafts result in increased BMP4 mRNA levels that are accompanied by decreased expression of the extracellular BMP inhibitor noggin [13]. In this study, we evaluated the in vivo expression of BMP4 in mice after carotid ligation.…”

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confidence: 99%

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Endothelial Bmp4 Is Induced During Arterial Remodeling: Effects on Smooth Muscle Cell Migration and Proliferation

Corriere

Rogers

Eliason

et al. 2008

Journal of Surgical Research

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Background-Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily of proteins that have multiple functional roles in mammalian development. A role for BMP4 in adult vascular remodeling has recently been suggested. We evaluated the expression of Bmp4 during neointimal lesion development in vivo. We then assessed the role BMP4 signaling on SMC function during neointimal lesion development.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Endothelial Bmp4 Is Induced During Arterial Remodeling: Effects on Smooth Muscle Cell Migration and Proliferation

Corriere

Rogers

Eliason

et al. 2008

Journal of Surgical Research

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“…The expression of BMP2 and/or BMP4 in endothelial cells is significantly increased under various endothelial injurious conditions, including high flow shear stress (16), oscillatory shear stress (41), hyperhomocysteinemia (49), or treatment with H 2 O 2 (41), tumor necrosis factor-␣ (41), or hypoxia (5). The increased expression of BMPs under some of these conditions was found to mediate an inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice

Song

Coleman²,

Shi³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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. Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice. Am J Physiol Heart Circ Physiol 295: H677-H690, 2008. First published June 13, 2008 doi:10.1152/ajpheart.91519.2007.-Heterozygous bone morphogenetic protein receptor-II-knockout (BMPR2 ϩ/Ϫ ) mice have a similar genetic trait like that in some idiopathic pulmonary arterial hypertension patients. To examine the effect of pulmonary endothelial injury in BMPR2ϩ/Ϫ mice, we challenged the mice with two injections of monocrotaline combined with intratracheal instillation of replicationdeficient adenovirus expressing 5-lipoxygenase (MCTϩAd5LO). After the challenge (1 wk), BMPR2 ϩ/Ϫ mice exhibited a doubling of right ventricular systolic pressure that was greater than that of wildtype mice and remained elevated for 3 wk before heart failure developed. Muscularization and thickening of small pulmonary arterioles was evident in the BMPR2 ϩ/Ϫ lungs at 2 wk after the challenge and became severe at 3 wk. Marked perivascular infiltration of T cells, B cells, and macrophages was associated with the remodeled vessels. Real-time PCR analysis showed that the expression of six endothelial cell markers in lung tissue was decreased to 20 -40% of original levels at 1 wk after the challenge in both BMPR2ϩ/Ϫ and wild-type mice and largely recovered in wild-type (50 -80%) but not BMPR2 ϩ/Ϫ lungs (30 -50%) at 3 wk after the challenge. Macrophage inflammatory protein-1␣ and fractalkine receptor expression doubled in BMPR2ϩ/Ϫ compared with wild-type lungs. Expression of type I and type II BMP receptors, but not transforming growth factor-␤ receptors, in the challenged BMPR2 ϩ/Ϫ and wild-type lungs showed a similar pattern of expression as that of endothelial markers. Apoptotic responses at 1 wk after MCT and Ad5LO challenge were also significantly greater in the BMPR2 ϩ/Ϫ lungs than the wild-type lungs. These data show that BMPR2 ϩ/Ϫ mice are more sensitive to MCTϩAd5LO-induced pulmonary hypertension than wild-type mice. Greater endothelial injury and an enhanced inflammatory response could be the underlying causes of the sensitivity and may work in concert with BMPR2 heterozygosity to promote the development of persistent pulmonary hypertension.heterozygous bone morphogenetic protein receptor-2 knockout mice HETEROZYGOUS GERMLINE MUTATIONS of bone morphogenetic protein receptor-2 (BMPR2) have been found in patients with idiopathic pulmonary arterial hypertension (IPAH) (10,20,46), a progressive disease characterized by extensive remodeling of the pulmonary arterioles and persistent increase of pulmonary artery pressure of unknown cause. Nearly 70% of familial IPAH and 20% of sporadic IPAH patients have a heterozygous BMPR2 mutation (1), but the chance of developing pulmonary arterial hypertension (PAH) among the BMPR2 mutant family members is only 10 -20% (32). Therefore, additional factors are believed to be required for the development of PAH in the BMPR2 mutant carriers.The BMPR2 gene encodes BMPR-II, which forms a complex with ...

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“…Clinical studies report that VSMCs mainly localize in the distal region of the vascular stenosis with low shear stress [128][129][130]. Increasing blood flow in vessel grafts induces endothelialization and inhibits neointimal hyperplasia [125,131], the molecular mechanism of which is based on the high expression of bone morphogenic proteins (BMP4) [132] and NO [123]. However, segments of the artery wall exposed to lower endothelial shear stress are significantly thicker than segments exposed to higher shear stress within the same artery [133].…”

mentioning

confidence: 99%

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

Qiu

Zheng

et al. 2014

J. R. Soc. Interface.

149

115

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Vascular smooth muscle cells (VSMCs) have critical functions in vascular diseases. Haemodynamic factors are important regulators of VSMC functions in vascular pathophysiology. VSMCs are physiologically active in the threedimensional matrix and interact with the shear stress sensor of endothelial cells (ECs). The purpose of this review is to illustrate how haemodynamic factors regulate VSMC functions under two-dimensional conditions in vitro or three-dimensional co-culture conditions in vivo. Recent advances show that high shear stress induces VSMC apoptosis through endothelial-released nitric oxide and low shear stress upregulates VSMC proliferation and migration through platelet-derived growth factor released by ECs. This differential regulation emphasizes the need to construct more actual environments for future research on vascular diseases (such as atherosclerosis and hypertension) and cardiovascular tissue engineering.

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Bone morphogenetic protein 4: Potential regulator of shear stress-induced graft neointimal atrophy

Abstract: Increased BMPs (particularly BMP4) coupled with decreased noggin may promote high shear stress-mediated graft neointimal atrophy by inhibiting SMC proliferation and increasing SMC death.

Cited by 23 publications

References 62 publications

Endothelial Bmp4 Is Induced During Arterial Remodeling: Effects on Smooth Muscle Cell Migration and Proliferation

Endothelial Bmp4 Is Induced During Arterial Remodeling: Effects on Smooth Muscle Cell Migration and Proliferation

Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

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