A successful experimental model for intimal hyperplasia prevention using a resveratrol-delivering balloon

Tolva, Valerio; Mazzola, Silvia; Zerbi, Pietro; Casana, Renato; Albertini, M.; Calvillo, Laura; Selmin, Francesca; Cilurzo, Francesco

doi:10.1016/j.jvs.2014.09.035

Cited by 16 publications

(26 citation statements)

References 16 publications

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“…Another subject of the current investigation is resveratrol, the additive to paclitaxel. Previous comprehensive experiments and published data [ 20 – 24 ] suggest resveratrol to be a useful coating additive. The primary purpose of the additive is to modulate adherence and release of the drug.…”

Section: Discussionmentioning

confidence: 99%

Drug Distribution and Basic Pharmacology of Paclitaxel/Resveratrol-Coated Balloon Catheters

Speck

Häckel

Schellenberger

et al. 2018

Cardiovasc Intervent Radiol

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PurposeTo experimentally investigate a new homogenously paclitaxel/resveratrol-coated balloon catheter in terms of transport of the coating to the treated tissue and local effects including histology and functional tests.MethodsAdherence of the coating to the balloon was explored by in vitro simulation of its passage to the lesion. Paclitaxel and resveratrol transfer to the vessel wall was investigated in porcine coronary and peripheral arteries. Matrix-assisted laser desorption/ionization (MALDI) was used for direct microscopic visualization of paclitaxel in arterial tissue. Inhibition of neointimal proliferation and tolerance of complete coating and resveratrol-only coating was investigated in pigs 4 weeks after treatment, and the effect of resveratrol on inflammation and healing after 3 and 7 days.ResultsDrug loss on the way to the lesion was < 10% of dose, while 65 ± 13% was detected at the site of balloon inflation. After treatment similar proportions of drug were detected in coronary and peripheral arteries, i.e., 7.4 ± 4.6% of dose or 125 ± 74 ng/mg tissue. MALDI showed circumferential deposition. Inhibition of neointimal proliferation by paclitaxel/resveratrol coating was significant (p = 0.001) whereas resveratrol-only coating did not inhibit neointimal proliferation. During the first week after treatment of peripheral arteries with resveratrol-only balloons, we observed nominally less inflammation and fibrin deposition along with a significant macrophage reduction and more pronounced re-endothelialization. No safety issues emerged including left ventricular ejection fraction for detection of potential distal embolization after high-dose treatment of coronary arteries.ConclusionsPaclitaxel/resveratrol-coated balloons were effective and safe in animal studies. Beyond acting as excipient resveratrol may contribute to vascular healing.

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Section: Discussionmentioning

confidence: 99%

Drug Distribution and Basic Pharmacology of Paclitaxel/Resveratrol-Coated Balloon Catheters

Speck

Häckel

Schellenberger

et al. 2018

Cardiovasc Intervent Radiol

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“…In preclinical studies, oral administration of resveratrol at 4 mg/kg/day reduced significantly the proliferation of smooth muscle cells, hyperplasia of endothelial vessels as well as the secretion of pro-inflammatory cytokines involved in the atherogenesis process [101]. Notably, another cardiovascular outcome associated with the administration of resveratrol in preclinical studies is the reduction of intimal proliferation index (ratio of intimal to (intimal + medial) area) of 45-50% compared to control animals with a significant reduction of α-actin expression in intima [102]. The main mediators of these effects are p53, heat shock protein HSP27, quinone reductases as well as nitric oxide [102].…”

Section: Resveratrol In Cardio-oncologymentioning

confidence: 99%

“…Notably, another cardiovascular outcome associated with the administration of resveratrol in preclinical studies is the reduction of intimal proliferation index (ratio of intimal to (intimal + medial) area) of 45-50% compared to control animals with a significant reduction of α-actin expression in intima [102]. The main mediators of these effects are p53, heat shock protein HSP27, quinone reductases as well as nitric oxide [102]. Considering that several cancer therapies like androgen deprivation therapy are conceived to indirectly contribute to the development of hyperglycemia, dyslipidemia and metabolic syndrome, which are well-established causal risk factors of atherosclerosis [103,104], the use of resveratrol in this category of patients could be a therapeutic window of interest in the cardio-oncological field.…”

Section: Resveratrol In Cardio-oncologymentioning

confidence: 99%

Resveratrol in Cancer Patients: From Bench to Bedside

Berretta

Bignucolo

Francia

et al. 2020

IJMS

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Resveratrol (3,5, is a natural phytoalexin that accumulates in several vegetables and fruits like nuts, grapes, apples, red fruits, black olives, capers, red rice as well as red wines. Being both an extremely reactive molecule and capable to interact with cytoplasmic and nuclear proteins in human cells, resveratrol has been studied over the years as complementary and alternative medicine (CAM) for the therapy of cancer, metabolic and cardiovascular diseases like myocardial ischemia, myocarditis, cardiac hypertrophy and heart failure. This review will describe the main biological targets, cardiovascular outcomes, physico-chemical and pharmacokinetic properties of resveratrol in preclinical and clinical models implementing its potential use in cancer patients.properties of resveratrol are, however, marked by a pharmacokinetic profile and by an unfavorable oral bioavailability, which requires a thorough analysis. To date, to the best of our knowledge, scientific papers and reviews summarizing multiple characteristics of resveratrol, its pharmacokinetic, pharmacodynamic profiles and potential drug interaction in oncology are lacking in literature. Therefore, this review aimed to describe the potential use of resveratrol in cancer management presenting the main biochemical pathways involved, issues and potential uses in cancer patients. Moreover, the involvement of resveratrol in cardioncology, its potential use for risk reduction of myocardial ischemia, myocarditis, cardiac hypertrophy as well as heart failure are also discussed. To endorse this review, we made a comprehensive search on PubMed, Web of Science and SciFinder. The search terms were "resveratrol" combined with "cardioncology" or "cancer" or "drug-food" or "cardiology" or "pharmacokinetic" or "pharmacodynamic". Physico-Chemical and Pharmacokinetic Properties of ResveratrolResveratrol is a low molecular weight phyto-polyphenol of 228 Da that appears as an off-white powder with lipophilic properties (octanol/water partition coefficient, log Kow = 3.1). Its melting point is between 253 and 255 • C, and its solubility in water is very low (3 mg/100 mL) [8]. The ethylene bridge due to a limited degree of freedom generates two geometric isomers: cis-resveratrol and trans-resveratrol ( Figure 1) [5]. These isoforms co-exist in resveratrol extracts even if a greater biological activity and stability are attributed to trans-resveratrol. Comparing to the geometric isomers, the nearly planar structure of trans-resveratrol is less flexible than the non-planar structure of cis-resveratrol, but it possesses a lower repulsive energy that ensures it, albeit small, higher stability. Isomerization of trans-resveratrol to cis-resveratrol occurs via molecule breakdown when trans-resveratrol is exposed to UV radiation at a wavelength of 254 or 366 nm, to high pH conditions or in plants during fermentation processes [5,9]. In analyzing some physical-chemical aspects of resveratrol, Zupancic et al. showed how trans-resveratrol is rapidly degradable in high-pH solutions. In par...

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“…For example, following vascular injury various cytokines, including PDGF-BB, are released by endothelial cells and macrophages. These stimulate the abnormal proliferation and migration VSMCs, a key promoter in the initiation of intimal hyperplasia, which can further lead to arteriosclerosis and restenosis following PCI (20)(21)(22). Therefore, inhibition of PDGF-BB-induced VSMCs proliferation and migration is crucial for the prevention of atherosclerosis and restenosis.…”

Section: Discussionmentioning

confidence: 99%

Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells

Chen

Liu

Cai

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus, has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia-induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with formononetin significantly inhibited PDGF-BB-induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of formononetin suppressed PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with formononetin inhibited the PDGF-BB-induced upregulation of cell cycle-related proteins, matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of formononetin inhibited the phosphorylation of AKT induced by PDGF-BB in VSMCs. The present results suggest that formononetin has a suppressive effect on PDGF-BB-stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore, formononetin may be useful for the treatment of intimal hyperplasia, atherosclerosis and restenosis.

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A successful experimental model for intimal hyperplasia prevention using a resveratrol-delivering balloon

Cited by 16 publications

References 16 publications

Drug Distribution and Basic Pharmacology of Paclitaxel/Resveratrol-Coated Balloon Catheters

Drug Distribution and Basic Pharmacology of Paclitaxel/Resveratrol-Coated Balloon Catheters

Resveratrol in Cancer Patients: From Bench to Bedside

Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells

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