Ischemia depletes dystrophin and inhibits protein synthesis in the canine heart:Mechanisms of myocardial ischemic injury

Rodrı́guez, Manuel; Cai, Wenju; Kostin, Sawa; Lucchesi, Benedict R.; Schaper, Jutta

doi:10.1016/j.yjmcc.2005.02.019

Cited by 49 publications

(49 citation statements)

References 32 publications

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“…Its expression is down-regulated in various diseases, including dystrophinopathies and ischemic heart disease [8,[20][21][22][23][24]. In contrary to the results obtained by Spier et al [28], we noted a lower staining intensity and percentage of DMD--immunoreactive cells in the DCM dogs as compared to control group.…”

Section: Sarcomeric Actinin and Smacontrasting

confidence: 99%

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Cardiomyocyte marker expression in dogs with left atrial enlargement due to dilated cardiomyopathy or myxomatous mitral valve disease

Janus

Kandefer-Gola

Ciaputa

et al. 2017

Folia Histochem Cytobiol.

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Introduction. Dilated cardiomyopathy (DCM) and myxomatous mitral valve disease (MMVD) are common heart conditions in dogs. They have different etiology and pathogenesis and although other studies focused on changes in the left ventricles of the affected hearts, the aim of our study was to assess the expressions of some intrinsic proteins in the enlarged left atria. Material and methods. We performed an immunohistochemical analysis of left atrial specimens obtained from 15 dogs with DCM, 35 dogs with MMVD and six control dogs. We assessed the expression of following proteins: SERCA1, SERCA2, sarcomeric actinin, smooth muscle actin, and dystrophin. Results. We noted a higher percentage of SERCA1-positive cells in the MMVD group and lower percentage of dystrophin-positive cells in the DCM group as compared to control group. The expression of other proteins was similar in the hearts of control dogs and dogs with heart diseases. Conclusions. The observed changes in the expression patterns of some proteins in the atria of dogs with DCM and MMVD suggest that atrial enlargement relies not only on volume overload, but also alterations of the intrinsic proteins can contribute to the pathogenesis of dilated cardiomyopathy.

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Section: Sarcomeric Actinin and Smacontrasting

confidence: 99%

“…In the disease, the heart muscle is mechanically weak and the contraction of the cell leads to membrane damage, muscle necrosis and degeneration [8,[20][21][22]. Apart from being a cause of muscle diseases, DMD was also found to be down-regulated in consequence of myocardial injury and ischemia of various origins [23,24].…”

Section: Introductionmentioning

confidence: 99%

Cardiomyocyte marker expression in dogs with left atrial enlargement due to dilated cardiomyopathy or myxomatous mitral valve disease

Janus

Kandefer-Gola

Ciaputa

et al. 2017

Folia Histochem Cytobiol.

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“…In general, the conjugation causes the reduction in the bioactivity of ROP; however, well preserved bioactivity is observed when the grafting degree of the conjugate is lower. In another study, it was found that due to the enhanced permeability and retention (EPR) effect caused by ischemia, 11,12 the distribution of ROP (∼2 nm) is approximately twofold higher in myocardial ischemic rat hearts than in normal ones. 13 However, the utilization of the EPR effect is significantly limited by the rapid glomerular filtration of ROP, making the increase far from ideal.…”

Section: Introductionmentioning

confidence: 99%

Long-circulating delivery of bioactive polysaccharide from radix ophiopogonis by PEGylation

Lin

Wang²,

Huang³

et al. 2011

IJN

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Background: Radix ophiopogonis polysaccharide (ROP) has been found to be effective against myocardial ischemia. One of main problems with its use is its short in-vivo half-life, which makes the development of an effective delivery system necessary. To achieve better therapeutic effects and patient compliance by prolonging its retention in plasma and increasing its distribution in targets, ROP was PEGylated (PEG, polyethylene glycol) in this study. Methods: Through a moderate coupling reaction between hydroxyl-activated ROP and aminoterminated methoxy-PEG (mPEG) (30 or 40 kDa), together with a greater than 1 molar ratio of ROP to mPEG in reaction, long-circulating and potentially bioactive PEGylated ROPs, with PEG grafting number of ∼1.0, were prepared, characterized, and the pharmacokinetics evaluated. Results: Relative to ROP, whose half-life was approximately 0.7 hours, the two conjugates prepared, following intravenous administration, showed markedly prolonged retention in systemic circulation with half-lives in blood of 78.4 and 88.3 hours, respectively. When given subcutaneously, their in-vivo mean residence times were further markedly prolonged by the slow absorption phase. They were found to be well absorbed after subcutaneous administration, with absolute bioavailability being 75.4% and 43.9%, respectively. Conclusion: With apparent molecular masses not exceeding 43 kDa, the conjugates prepared have been and will be demonstrated to have prominent advantages for ROP delivery, such as: the good absorption following subcutaneous, intramuscular, or other ways of administration; the effective utilization of the enhanced permeability and retention effect caused by ischemia; and the rapid diffusion within target tissues.

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“…On the other hand, it causes some targeting-facilitated pathophysiological changes, especially the enhanced permeability and retention (EPR) effect. 7,8 Both various nano-sized insoluble drug delivery systems (eg, liposomes, micelles, nanoparticles, microbubbles, and cell ghosts) and soluble polymeric drugs are now used to target parenteral drugs to ischemic myocardia by the EPR effect alone or in combination with certain active and/or physicochemical targeting mechanism/ mechanisms. [9][10][11] By comparison, polymeric drugs, which generally have a smaller size than the former, could achieve the longer retention time in the blood and higher drug stability, as well as better drug release and targeting behaviors.…”

Section: Introductionmentioning

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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Ischemia depletes dystrophin and inhibits protein synthesis in the canine heart:Mechanisms of myocardial ischemic injury

Cited by 49 publications

References 32 publications

Cardiomyocyte marker expression in dogs with left atrial enlargement due to dilated cardiomyopathy or myxomatous mitral valve disease

Cardiomyocyte marker expression in dogs with left atrial enlargement due to dilated cardiomyopathy or myxomatous mitral valve disease

Long-circulating delivery of bioactive polysaccharide from radix ophiopogonis by PEGylation

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

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Ischemia depletes dystrophin and inhibits protein synthesis in the canine heart:Mechanisms of myocardial ischemic injury

Cited by 49 publications

References 32 publications

Cardiomyocyte marker expression in dogs with left atrial enlargement due to dilated cardiomyopathy or myxomatous mitral valve disease

Cardiomyocyte marker expression in dogs with left atrial enlargement due to dilated cardiomyopathy or myxomatous mitral valve disease

Long-circulating delivery of bioactive polysaccharide from radix ophiopogonis by PEGylation

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

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