A New Intra-Arterial DeliveryPlatform for Pro-Arteriogenic Compounds to Stimulate Collateral Artery Growth Via Transforming Growth Factor-β1 Release

Grundmann, Sebastian; Royen, Niels van; Pasterkamp, Gérard; Gonzalez, N. Vazquez; Tijsma, E.; Piek, Jan J.; Hoefer, Imo E.

doi:10.1016/j.jacc.2007.03.046

Cited by 25 publications

(19 citation statements)

References 25 publications

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“…Our research group has a longstanding interest in the regulation of blood vessel growth, and we use the hindlimb ischemia model as one of several in vivo models. 19,20 To identify novel regulators of neovascularization, we aimed to unravel the temporal changes of miRNA expression in the widely used neovascularization model of murine femoral artery ligation. Our microarray screen yielded many differentially expressed miRNAs of potential interest, among them several with a previously described regulatory function in blood vessel growth.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-100 Regulates Neovascularization by Suppression of Mammalian Target of Rapamycin in Endothelial and Vascular Smooth Muscle Cells

Grundmann¹,

Hans²,

Kinniry³

et al. 2011

Circulation

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177

143

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Background— The adaptive growth of blood vessels is an important protective mechanism in cardiovascular disease. However, the underlying regulatory mechanisms of this process are only partly understood. Recently, small endogenous RNAs (microRNAs [miRNAs]) were found to play an important role in embryonic and postnatal vascular development. Here, we used miRNA transcriptome analysis after induction of hind-limb ischemia in mice to screen for miRNAs involved in adaptive blood vessel growth following arterial occlusion. Methods and Results— Using miRNA arrays, we explored the miRNA expression profile during adaptive neovascularization. We describe specific changes in miRNA expression patterns and show that miRNA-100 is significantly downregulated after induction of hind-limb ischemia in mice. Our data demonstrate that miR-100 modulates proliferation, tube formation, and sprouting activity of endothelial cells and migration of vascular smooth muscle cells and functions as an endogenous repressor of the serine/threonine protein kinase mammalian target of rapamycin (mTOR). Whereas miR-100 inhibition increased mTOR levels in endothelial cells, overexpression of miR-100 reduced mTOR expression and consequently attenuated cellular proliferation. Supporting this notion, overexpression of an mTOR construct lacking the miRNA binding site rescued the inhibitory effect of miR-100 on cell proliferation. Accordingly, miR-100 inhibition by specific antagomirs in vivo stimulated angiogenesis and resulted in functional improvement of perfusion after femoral artery occlusion in mice. In contrast, treatment with the mTOR inhibitor rapamycin had the opposite effect. Conclusions— Our data demonstrate that miR-100 has an antiangiogenic function and represses mTOR signaling in endothelial and vascular smooth muscle cells. Inhibition of miR-100 could be a novel approach for the modulation of blood vessel growth and other mTOR-dependent processes.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-100 Regulates Neovascularization by Suppression of Mammalian Target of Rapamycin in Endothelial and Vascular Smooth Muscle Cells

Grundmann¹,

Hans²,

Kinniry³

et al. 2011

Circulation

Self Cite

177

143

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“…Implantation of TGF-β1-eluting stent almost doubled collateral conductance relative to a single bolus infusion of the same dose of TGF-β1, which displayed negligible effects on collateral artery growth. In addition, TGF-β1-eluting stents induced only localized effects as opposed to systemic increases in TGF-β1 plasma levels [92]. This study highlights that the exposure time for some pro-arteriogenic compounds can lead to varying therapeutic effects, even with equal doses.…”

Section: Mode Of Administration Of Pro-arteriogenic Compoundsmentioning

confidence: 97%

“…Local intra-arterial delivery of pro-arteriogenic compounds over a prolonged period of time displays greater efficacy than other modes of administration, including intravenous, intramuscular, subcutaneous or intrapericardial infusion [90-92]. …”

Section: Mode Of Administration Of Pro-arteriogenic Compoundsmentioning

confidence: 99%

“…[92], a direct comparison was made between slow intra-arterial elution of transforming growth factor (TGF)-β1 by stent elution with a single intra-arterial bolus injection of the same dosage of TGF-β1 in a rabbit hind limb ischemia model. Implantation of TGF-β1-eluting stent almost doubled collateral conductance relative to a single bolus infusion of the same dose of TGF-β1, which displayed negligible effects on collateral artery growth.…”

Section: Mode Of Administration Of Pro-arteriogenic Compoundsmentioning

confidence: 99%

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The Future of Collateral Artery Research

Hakimzadeh¹,

Verberne²,

Siebes³

et al. 2014

CCR

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In the event of obstructive coronary artery disease, collateral arteries have been deemed an alternative blood source to preserve myocardial tissue perfusion and function. Monocytes play an important role in modulating this process, by local secretion of growth factors and extracellular matrix degrading enzymes. Extensive efforts have focused on developing compounds for augmenting the growth of collateral vessels (arteriogenesis). Nonetheless, clinical trials investigating the therapeutic potential of these compounds resulted in disappointing outcomes. Previous studies focused on developing compounds that stimulated collateral vessel growth by enhancing monocyte survival and activity. The limited success of these compounds in clinical studies, led to a paradigm shift in arteriogenesis research. Recent studies have shown genetic heterogeneity between CAD patients with sufficient and insufficient collateral vessels. The genetic predispositions in patients with poorly developed collateral vessels include overexpression of arteriogenesis inhibiting signaling pathways. New directions of arteriogenesis research focus on attempting to block such inhibitory pathways to ultimately promote arteriogenesis. Methods to detect collateral vessel growth are also critical in realizing the therapeutic potential of newly developed compounds. Traditional invasive measurements of intracoronary derived collateral flow index remain the gold standard in quantifying functional capacity of collateral vessels. However, advancements made in hybrid diagnostic imaging modalities will also prove to be advantageous in detecting the effects of pro-arteriogenic compounds.

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“…Despite progress in revascularization procedures, a substantial number of patients are not candidates for these procedures [1]. Stimulation of angiogenesis by exogenous growth factor administration or gene transfer has emerged as an alternative strategy to salvage ischemic cardiac and skeletal muscles [2,3]. Although initial trials involving the delivery of angiogenic factors, such as vascular endothelial growth factor-A (VEGF-A), were associated with short-term improvement, follow-up studies have yet to show long-term benefits [4].…”

Section: Introductionmentioning

confidence: 99%

Models for the Study of Angiogenesis

Shiba

Takahashi²,

Ikeda³

2008

CPD

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Cardiovascular disease remains a principal cause of mortality in Western countries. Novel strategies for enhancing angiogenesis (such as gene or cell therapy) provide alternative choices for patients without any current treatment options. This progress has contributed towards understanding the mechanisms underlying vascular formation. The establishment of new experimental models could lead to the development of new treatments. This article overviews the diverse models for the study of angiogenesis.

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A New Intra-Arterial DeliveryPlatform for Pro-Arteriogenic Compounds to Stimulate Collateral Artery Growth Via Transforming Growth Factor-β1 Release

Cited by 25 publications

References 25 publications

MicroRNA-100 Regulates Neovascularization by Suppression of Mammalian Target of Rapamycin in Endothelial and Vascular Smooth Muscle Cells

MicroRNA-100 Regulates Neovascularization by Suppression of Mammalian Target of Rapamycin in Endothelial and Vascular Smooth Muscle Cells

The Future of Collateral Artery Research

Models for the Study of Angiogenesis

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