Effect of hypercholesterolaemia on myocardial function, ischaemia–reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning

Andreadou, Ioanna; Iliodromitis, Efstathios K.; Lazou, Antigone; Görbe, Anikó; Giricz, Zoltán; Schulz, Rainer; Ferdinándy, Péter

doi:10.1111/bph.13704

Cited by 66 publications

(57 citation statements)

References 120 publications

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“…It renders the heart to increased oxidative stress, mitochondrial dysfunction, and inflammation triggered apoptosis. All these changes increase the susceptibility of the heart to infarction [95].…”

Section: Effects Of Tocotrienol On Cardiovascular Diseasesmentioning

confidence: 99%

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

et al. 2020

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Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, as well as cancers. Studies showed that T3 could prevent various NCDs, by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the mevalonate pathway, inflammatory response, oxidative stress, and alternating hormones. The efficacy of T3 in preventing/treating these NCDs is similar or greater compared to tocopherol (TF). TF may lower the efficacy of T3 because the efficacy of the combination of TF and T3 was lower than T3 alone in some studies. Data investigating the effects of T3 on osteoporosis, arthritis, and peptic ulcers in human are limited. The positive outcomes of T3 treatment obtained from the preclinical studies warrant further validation from clinical trials.Nutrients 2020, 12, 259 2 of 84 Nutrients 2020, 12, 259 4 of 84 the order δ > γ > β > α [45]. Using HepG2 cells, γT3 was shown to stimulate apolipoprotein B (Apo-B) degradation by decreasing its translocation into the endoplasmic reticulum (ER) lumen. This action eventually caused a reduction in the number of Apo-B in lipoprotein particles [46]. Other reports showed that γT3 and δT3 had the potential to reduce the hepatic TG synthesis and very-low-density lipoprotein (VLDL) secretion by suppressing expression of genes involved in lipid homeostasis, particularly the TG, cholesterol, and VLDL biosynthesis. Moreover, δT3 also promoted the efflux of LDL through LDL receptor expression [47]. A summary of the literature on effect of T3 supplementation on lipid profile of hypercholesterolemic model in vitro is shown in Table 1.Animal models of dyslipidemia have been used to investigate the effects of T3 on lipid profile. Several animals have been tested, including chicken, swine and rodents (rats, hamsters, guinea pigs). In chickens fed with a varying level of αTF and γT3, Qureshi et al. (1996) showed that αTF enhanced the inhibition of HMGCR by γT3. They further stipulated that the vitamin E mixture should contain 15-20% of αTF and approximately 60% of γT3 or δT3 for optimal anti-cholesterol effects [48]. In the subsequent study, demonstrated that combination of 50 ppm T3-rich fraction (TRF) and 50 ppm lovastatin was more effective in suppressing HMGCR activity compared to lovastatin alone in chickens. The combination also reduced serum TC and LDL-C, TG, Apo-B, thromboxane B 2 , and platelet factor 4 in contrast to individual treatment [49]. Using chicken supplemented with 50 ppm of δT3, Qureshi et al. (2011) further revealed that δT3 reduced TC and LDL-C besides suppressing the lipid elevating effects of dexamethasone and potentiated the TG-lowering effect of riboflavin [50]. Using genetically hypercholesterolemic swine, Qureshi et al. (1991) demonstrated the significant effect of TRF in lowering serum TC, LDL-C, Apo-B, thrombo...

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Section: Effects Of Tocotrienol On Cardiovascular Diseasesmentioning

confidence: 99%

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

et al. 2020

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“…In addition, the protective effect of ischemic postconditioning is comparable with that of IP. On the other hand, accumulating evidence has shown that drug treatments for ischemic myocardium at the onset of reperfusion (e.g., pharmacological postconditioning) are capable of providing a similar protective effect with ischemic postconditioning [6-9]. Pharmacological postconditioning represents an ideal alternative for ischemic postconditioning since its clinical operation is simpler than ischemic postconditioning.…”

Section: Introductionmentioning

confidence: 99%

ω-3 Polyunsaturated Fatty Acid Postconditioning Protects the Isolated Perfused Rat Heart from Ischemia-Reperfusion Injury

et al. 2018

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Aims: This study aimed to evaluate the cardioprotective effects of ω-3 polyunsaturated fatty acids (PUFAs) postconditioning against ischemia-reperfusion (I/R) injury. Methods: Sixty Sprague-Dawley rats were randomly divided into 4 groups (n = 15 for each) and used to generate the Langendorff isolated perfused rat heart model. The sham group received a continuous perfusion of 150 min. The remaining three I/R-treated groups sequentially received a 30-min perfusion, a 30-min cardioplegia, and a 90-min reperfusion. The I/R-ischemic preconditioning (IP) group additionally received three cycles of 20-s reperfusion and 20-s coronary reocclusion preceded the 90 min of reperfusion. The I/R-ω group were perfused with ω-3 PUFAs for 15 min before the 90 min of reperfusion. The myocardial infarct size, the degree of mitochondrial damage, the antioxidant capacity of the myocardium, and the cardiac functions during reperfusion were compared among groups. Results: Compared with the I/R group, the I/R-ω group had significantly reduced myocardial infarct size, reduced levels of lactate dehydrogenase and malondialdehyde, elevated superoxide dismutase level, and elevated rising (+dp/dt_max) and descending (–dp/dt_max) rate of left ventricular pressure. The I/R-ω group had a significantly lower rate of mitochondrial damage in myocardial tissue compared with the I/R and I/R-IP groups. Conclusion: ω-3 PUFA postconditioning possesses good cardioprotective effects and may be developed into a therapeutic strategy for myocardial I/R injury.

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“…A separate but related issue that may also impede clinical translation of RIPC is the confounding role of co‐morbidities. For example, hypercholesterolaemia (Kocic, Konstanski, Kaminski, Dworakowska, & Dworakowski, ; Ueda et al ., ) and diabetes (Kristiansen et al., ; Przyklenk, Maynard, Greiner, & Whittaker, ; Tsang, Hausenloy, Mocanu, Carr, & Yellon, ; Whittington et al., ) have been shown to interfere with the efficacy of classic ischaemic preconditioning and postconditioning (Andreadou et al., ; Ferdinandy, Hausenloy, Heusch, Baxter, & Schulz, ; Przyklenk, ), and emerging data from a small number of studies suggest that the infarct‐sparing effect of RIPC may, similarly, be compromised in comorbid models (Ma et al., ; Wider et al., ). For example, Wider et al .…”

Section: Remote Ischaemic Pre‐conditioning – Trials Tribulations Andmentioning

confidence: 99%

Ischaemic and hypoxic conditioning: potential for protection of vital organs

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Przyklenk

et al. 2019

Experimental Physiology

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New Findings What is the topic of this review?Remote ischaemic preconditioning (RIPC) and hypoxic preconditioning as novel therapeutic approaches for cardiac and neuroprotection. What advances does it highlight?There is improved understanding of mechanisms and signalling pathways associated with ischaemic and hypoxic preconditioning, and potential pitfalls with application of these therapies to clinical trials have been identified. Novel adaptations of preconditioning paradigms have also been developed, including intermittent hypoxia training, RIPC training and RIPC–exercise, extending their utility to chronic settings. Abstract Myocardial infarction and stroke remain leading causes of death worldwide, despite extensive resources directed towards developing effective treatments. In this Symposium Report we highlight the potential applications of intermittent ischaemic and hypoxic conditioning protocols to combat the deleterious consequences of heart and brain ischaemia. Insights into mechanisms underlying the protective effects of intermittent hypoxia training are discussed, including the activation of hypoxia‐inducible factor‐1 and Nrf2 transcription factors, synthesis of antioxidant and ATP‐generating enzymes, and a shift in microglia from pro‐ to anti‐inflammatory phenotypes. Although there is little argument regarding the efficacy of remote ischaemic preconditioning (RIPC) in pre‐clinical models, this strategy has not consistently translated into the clinical arena. This lack of translation may be related to the patient populations targeted thus far, and the anaesthetic regimen used in two of the major RIPC clinical trials. Additionally, we do not fully understand the mechanism through which RIPC protects the vital organs, and co‐morbidities (e.g. hypercholesterolemia, diabetes) may interfere with its efficacy. Finally, novel adaptations have been made to extend RIPC to more chronic settings. One adaptation is RIPC–exercise (RIPC‐X), an innovative paradigm that applies cyclical RIPC to blood flow restriction exercise (BFRE). Recent findings suggest that this novel exercise modality attenuates the exaggerated haemodynamic responses that may limit the use of conventional BFRE in some clinical settings. Collectively, intermittent ischaemic and hypoxic conditioning paradigms remain an exciting frontier for the protection against ischaemic injuries.

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Effect of hypercholesterolaemia on myocardial function, ischaemia–reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning

Abstract: This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.

Cited by 66 publications

References 120 publications

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

ω-3 Polyunsaturated Fatty Acid Postconditioning Protects the Isolated Perfused Rat Heart from Ischemia-Reperfusion Injury

Ischaemic and hypoxic conditioning: potential for protection of vital organs

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