Targeting cell death in the reperfused heart: Pharmacological approaches for cardioprotection

Oerlemans, M. I. F. J.; Koudstaal, Stefan; Chamuleau, Steven A.J.; Kleijn, Dominique Pv de; Doevendans, Pieter A.; Sluijter, Joost P.G.

doi:10.1016/j.ijcard.2012.03.055

Cited by 103 publications

(83 citation statements)

References 211 publications

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“…Taking into consideration the following two factors -1) the increased vascular permeability caused by the IR injury persisted for at least 48 hours and gradually recovered within 2 weeks; 31 and 2) the therapeutic interventions proven to reduce the infarct size in both experimental and clinical models were often administered at the time of myocardial reperfusion 32 -the PEG-ROP conjugates were injected via the tail vein immediately after the IR surgery finished and were allowed to circulate for the predetermined amounts of time. For the rat model of MI, rats were subjected to prolonged periods of myocardial ischemia for 3 days without reperfusion.…”

Section: Yao Et Almentioning

confidence: 99%

Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats

Yao¹,

Shi²,

Lin³

et al. 2015

IJN

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Although PEGylation plays an important role in drug delivery, knowledge about the distribution behavior of PEGylated drugs in ischemic myocardia is rather limited compared to nanoparticles. This work therefore aims to characterize the targeting behavior of the anti-myocardial ischemic mono-PEGylated conjugates of Radix Ophiopogonis polysaccharide (ROP) in two clinically relevant animal models, ie, the myocardial infarction (MI) model and the ischemia/reperfusion (IR) model. To determine the effect of the molecular size of conjugates, two representative conjugates (20- and 40-kDa polyethylene glycol mono-modified ROPs), with hydrodynamic size being approximately and somewhat beyond 10 nm, respectively, were studied in parallel at three time points postdose after a method for determining them quantitatively in biosamples was established. The results showed that the cardiac distribution of the two conjugates was significantly enhanced in both MI and IR rats due to the enhanced permeability and retention effect induced by ischemia. In general, the cardiac targeting efficacy of the conjugates in MI and IR rats was approximately 2; however, different changing in targeting efficacy with time was observed between MI and IR rats and also between the conjugates. Although the enhanced permeability and retention effect-based targeting efficacy for mono-PEGylated ROPs was not high, they, as dissolved macromolecules, are prone to diffusion in the cardiac interstitium space, and thus, facilitate the drug to reach perfusion-deficient and nonperfused areas. These findings are helpful in choosing the cardiac targeting strategy.

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Section: Yao Et Almentioning

confidence: 99%

Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats

Yao¹,

Shi²,

Lin³

et al. 2015

IJN

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“…e acute oxygen deprivation causes cardiomyocyte death via both apoptosis and necrosis, [10] which will trigger an in�ammatory response [11] that contributes to the removal of cell debris by proteolysis and phagocytosis. Subsequently, cardiac �broblasts in�ltrate the damaged tissue to increase the myocardial tensile strength via production of extracellular matrix in the infarct area and border zone.…”

Section: Cardiac Response To Injury and The Role Of Cell Therapymentioning

confidence: 99%

“…During, for example, acute myocardial infarction or the reperfused heart, loss of cardiomyocytes is mostly caused by apoptosis and necrosis. Several signal-transduction pathways are involved and many pharmacological targets are studied to limit ischemic cell death [10], for which oxidative stress and its effect on mitochondria, especially the mitochondrial permeability transition pore (MPTP), are very important. Apoptosis is a well-de�ned process by which the cell undergoes cell death following a variety of different stimuli, �nally resulting in the activation of caspases, whereas during regulated necrosis, or necroptosis, MPTP opening plays a central role.…”

Section: Mirnas In Cardiomyocyte Andmentioning

confidence: 99%

MicroRNAs in Cardiovascular Regenerative Medicine: Directing Tissue Repair and Cellular Differentiation

Sluijter

2013

ISRN Vascular Medicine

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MicroRNAs (miRNAs) are a class of short noncoding RNA molecules, approximately 22 nucleotides in length, which regulate gene expression through inhibition of the translation of target genes. It is now generally accepted that miRNAs guide processes and cellular functions through precise titration of gene dosage, not only for a single gene but also controlling the levels of a large cohort of gene products. miRNA expression is altered in cardiovascular disease and may thereby limit and impair cardiovascular repair responses. Increasing evidence of the essential role of miRNAs in the self-renewal and differentiation of stem cells suggests the opportunity of using the modulation of miRNA levels or their function in directing cell transplantation, cell behavior, and thereby organ healing. In this paper, an overview of miRNA biogenesis and their way of action and different roles that miRNAs play during the myocardial responses to injury and upon cell transplantation will be provided. We focused on cardiomyocyte survival, angiogenesis, extracellular matrix production, and how miRNAs can direct cell plasticity of injected cells and thus drive differentiation for cardiovascular phenotypes, including vascular differentiation and cardiomyocyte differentiation.

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“…Besides, difference in the severity of cardiac damage should also be a contributing factor. Considering that 1) the increased vascular permeability caused by the IR injury persisted for at least 48 hours and gradually recovered within 2 weeks 39 and 2) the therapeutic interventions proven to reduce the infarct size in both experimental and clinical models were often administered at the time of myocardial reperfusion; 40 each drug investigated here was injected via the tail vein immediately after the IR surgery finished. The ischemic degree was proven to be severe, and the average infarct size within 3-24 hours reperfusion was 37.2%±6.7% (n=10).…”

mentioning

confidence: 99%

Targeting delivery of Radix Ophiopogonis polysaccharide to ischemic/reperfused rat myocardium by long-circulating macromolecular and liposomal carriers

Wang¹,

Yao²,

et al. 2015

IJN

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Drug delivery to ischemic myocardium is an enormous challenge. This work aimed to characterize cardiac delivery behaviors of mono-polyethylene glycosylated (PEGylated) conjugates and long-circulating liposomes (L-Lps) with Radix Ophiopogonis polysaccharide (ROP) as drug. The results showed that compared to native ROP, 32-, 52-, and 45-fold increases in blood half-life were achieved by 20-kDa PEG mono-modified ROP (P 20k -R), 40-kDa PEG mono-modified ROP (P 40k -R), and ROP-loaded L-Lp, respectively. With comparable blood pharmacokinetics, ROP-loaded L-Lp showed both significantly higher targeting efficacy and drug exposure in infarcted myocardium than P 40k -R. With regard to P 20k -R, both its targeting efficacy and its level in infarcted myocardium at 3 hours postdose were comparable to P 40k -R, but its level in blood and myocardium reduced obviously faster. As a whole, the results indicate that both loading in L-Lps and mono-PEGylation are effective in targeting drug to ischemic myocardium, but the former appears to induce stronger effects.

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Targeting cell death in the reperfused heart: Pharmacological approaches for cardioprotection

Cited by 103 publications

References 211 publications

Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats

Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats

MicroRNAs in Cardiovascular Regenerative Medicine: Directing Tissue Repair and Cellular Differentiation

Targeting delivery of Radix Ophiopogonis polysaccharide to ischemic/reperfused rat myocardium by long-circulating macromolecular and liposomal carriers

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Targeting cell death in the reperfused heart: Pharmacological approaches for cardioprotection

Cited by 103 publications

References 211 publications

Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion&nbsp;rats

Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion&nbsp;rats

MicroRNAs in Cardiovascular Regenerative Medicine: Directing Tissue Repair and Cellular Differentiation

Targeting delivery of Radix Ophiopogonis polysaccharide to ischemic/reperfused rat myocardium by long-circulating macromolecular and liposomal carriers

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Product

Resources

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Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats

Increased cardiac distribution of mono-PEGylated Radix Ophiopogonis polysaccharide in both myocardial infarction and ischemia/reperfusion rats