Use of Nutraceuticals in Angiogenesis-Dependent Disorders

Morbidelli, Lucia; Terzuoli, Erika; Donnini, Sandra

doi:10.3390/molecules23102676

Cited by 20 publications

(16 citation statements)

References 102 publications

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“…The research exploring targets and molecules able to maintain EC physiological function and modulate or promote angiogenesis is ongoing. Our attention has been focused on natural products as nutraceuticals, since they promise to be a good source for prevention and therapeutic approaches in most of disorders associated with aberrant or non-functional vessels [32,33].…”

Section: Vascular Endothelium and Its Functionsmentioning

confidence: 99%

“…Polyphenols are a large group of biologically active molecules produced by plants and algae. Their effects on animals are multiple, and dependent on the intake dose and the circulating metabolites [32,33,122]. The list of plant-derived molecules also includes the toxins which at defined doses are used as cardiac drugs, such as digoxin.…”

Section: Influence Of Gut-derived Metabolites On Vascular Endothelmentioning

confidence: 99%

“…Based on the above findings, the topic is highly debated and research is ongoing to elucidate the proper composition and formulation of these very active compounds to be used in cardiovascular or metabolic disorders [32,33].…”

Section: Influence Of Gut-derived Metabolites On Vascular Endothelmentioning

confidence: 99%

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Circulating Metabolites Originating from Gut Microbiota Control Endothelial Cell Function

Amedei

Morbidelli

2019

Molecules

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Cardiovascular functionality strictly depends on endothelial cell trophism and proper biochemical function. Any condition (environmental, pharmacological/toxicological, physical, or neuro-humoral) that changes the vascular endothelium has great consequences for the organism’s wellness and on the outcome and evolution of severe cardiovascular pathologies. Thus, knowledge of the mechanisms, both endogenous and external, that affect endothelial dysfunction is pivotal to preventing and treating these disorders. In recent decades, significant attention has been focused on gut microbiota and how these symbiotic microorganisms can influence host health and disease development. Indeed, dysbiosis has been reported to be at the base of a range of different pathologies, including pathologies of the cardiovascular system. The study of the mechanism underlying this relationship has led to the identification of a series of metabolites (released by gut bacteria) that exert different effects on all the components of the vascular system, and in particular on endothelial cells. The imbalance of factors promoting or blunting endothelial cell viability and function and angiogenesis seems to be a potential target for the development of new therapeutic interventions. This review highlights the circulating factors identified to date, either directly produced by gut microbes or resulting from the metabolism of diet derivatives as polyphenols.

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Section: Vascular Endothelium and Its Functionsmentioning

confidence: 99%

Section: Influence Of Gut-derived Metabolites On Vascular Endothelmentioning

confidence: 99%

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Circulating Metabolites Originating from Gut Microbiota Control Endothelial Cell Function

Amedei

Morbidelli

2019

Molecules

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“…In particular, collateral vascular dysfunction is an important part of myocardial necrosis in the infarcted area (Thiagarajan et al, 2017). Vascular growth is in a relatively balanced state under normal conditions (Morbidelli et al, 2018). Under ischemia and hypoxia, the ability of vascular endothelial cells to divide, proliferate, and migrate is improved and angiogenesis is promoted (Thiagarajan et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Liraglutide Increases VEGF Expression via CNPY2-PERK Pathway Induced by Hypoxia/Reoxygenation Injury

Liu

et al. 2019

Front. Pharmacol.

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Liraglutide (Lir) is a glucagon-like peptide-1 receptor agonist that lowers blood sugar and reduces myocardial infarct size by improving endothelial cell function. However, its mechanism has not yet been clarified. Unfolded protein response (UPR) plays an important role in the pathogenesis of myocardial ischemia-reperfusion injury. It determines the survival of cells. Endoplasmic reticulum position protein homologue 2 (CNPY2) is a novel initiator of UPR that also participates in angiogenesis. To this extent, the current study further explored whether Lir regulates angiogenesis through CNPY2. In our article, a hypoxia/reoxygenation (H/R) injury model of human umbilical vein endothelial cells (HUVECs) was established and the effect of Lir on HUVECs was first evaluated by the Cell Counting Kit-8. Endothelial tube formation was used to analyze the ability of Lir to induce angiogenesis. Subsequently, the effect of Lir on the concentrations of hypoxia-inducible factor 1α (HIF1α), vascular endothelial growth factor (VEGF), and CNPY2 was detected by enzyme-linked immunosorbent assay. To assess whether Lir regulates angiogenesis through the CNPY2-initiated UPR pathway, the expression of UPR-related pathway proteins (CNPY2, GRP78, PERK, and ATF4) and angiogenic proteins (HIF1α and VEGF) was detected by reverse transcription-polymerase chain reaction and Western blot. The results confirmed that Lir significantly increased the expression of HIF1α and VEGF as well as the expression of CNPY2-PERK pathway proteins in HUVECs after H/R injury. To further validate the experimental results, we introduced the PERK inhibitor GSK2606414. GSK2606414 was able to significantly decrease both the mRNA and protein expression of ATF4, HIF1α, and VEGF in vascular endothelial cells after H/R injury. The effect of Lir was also inhibited using GSK2606414. Therefore, our study suggested that the CNPY2-PERK pathway was involved in the mechanism of VEGF expression after H/R injury in HUVECs. Lir increased the expression of VEGF through the CNPY2-PERK pathway, which may promote endothelial cell angiogenesis and protect HUVEC from H/R damage.

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“…Exploration of the biology of angiogenesis has led to the identification of new prognostic factors, tumor markers, and therapeutic approaches [75]. Prognostic biomarkers of angiogenesis (i.e., VEGF, SNPs) have the potential to provide an important contribution to AI therapies [76].…”

Section: Conclusion and Future Directionmentioning

confidence: 99%

Pharmacogenetic-Based Interactions between Nutraceuticals and Angiogenesis Inhibitors

Francia

Berretta

Benincasa

et al. 2019

Cells

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Background: Angiogenesis inhibitors (AIs) have become established as an effective cancer treatment. Whereas their interactions with antineoplastic drugs have extensively been investigated, little is known of the effect of their co-administration with nutraceuticals/dietary supplements (N/DSs), which are often self-prescribed. N/DSs comprise a wide range of products such as herbs, nutrients, vitamins, minerals, and probiotics. Assessment of their interactions with cancer drugs, particularly AIs, is hampered by the difficulty of gauging the amount of active substances patients actually take. Moreover, there is no agreement on which approach should be used to determine which N/DSs are most likely to influence AI treatment efficacy. We present a comprehensive review of the metabolic routes of the major AIs and their possible interactions with N/DSs. Methods: The PubMed and Cochrane databases were searched for papers describing the metabolic routes of the main AIs and N/DSs. Results: Data from the 133 studies thus identified were used to compile a diagnostic table reporting known and expected AI-N/DS interactions based on their metabolization pathways. AIs and N/DSs sharing the cytochrome P450 pathway are at risk of negative interactions. Conclusions: Recent advances in pharmacogenetics offer exceptional opportunities to identify prognostic and predictive markers to enhance the efficacy of individualized AI treatments. The table provides a guide to genotyping patients who are due to receive AIs and is a promising tool to prevent occult AI-N/DS interactions in poor metabolizers. N/DS use by cancer patients receiving AIs is a topical problem requiring urgent attention from the scientific community.

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Use of Nutraceuticals in Angiogenesis-Dependent Disorders

Cited by 20 publications

References 102 publications

Circulating Metabolites Originating from Gut Microbiota Control Endothelial Cell Function

Circulating Metabolites Originating from Gut Microbiota Control Endothelial Cell Function

Liraglutide Increases VEGF Expression via CNPY2-PERK Pathway Induced by Hypoxia/Reoxygenation Injury

Pharmacogenetic-Based Interactions between Nutraceuticals and Angiogenesis Inhibitors

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