Trimucrin, an Arg-Gly-Asp containing disintegrin, attenuates myocardial ischemia-reperfusion injury in murine by inhibiting platelet function

Hung, Ying; Kuo, Yu-Ju; Huang, Shiang‐Suo; Huang, Tur‐Fu

doi:10.1016/j.ejphar.2017.07.039

Cited by 11 publications

(8 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several animal studies in different species demonstrated beneficial effects of P-Selectin neutralization, e.g., via small molecule inhibition (38), chemical blockade (43), or antibody blocking (77) on IRI which were all associated with an antiplatelet effect accompanied by less neutrophil infiltration or platelet-neutrophil adhesion in the infarcted region. In addition to P-selectin, also platelet GPIIb/IIIa is claimed to contribute to postischemic leukocyte adhesion (36) and also the disintegrin-dependent attenuation of platelet induced myocardial IRI was shown to be accompanied by reduced neutrophil infiltration (41).…”

Section: Leukocyte-platelet-interactions In Irimentioning

confidence: 99%

Platelet Contributions to Myocardial Ischemia/Reperfusion Injury

2019

View full text Add to dashboard Cite

Obstruction of a coronary artery causes ischemia of heart tissue leading to myocardial infarction. Prolonged oxygen deficiency provokes tissue necrosis, which can result in heart failure and death of the patient. Therefore, restoration of coronary blood flow (reperfusion of the ischemic area) by re-canalizing the affected vessel is essential for a better patient outcome. Paradoxically, sudden reperfusion also causes tissue injury, thereby increasing the initial ischemic damage despite restoration of blood flow (=ischemia/reperfusion injury, IRI). Myocardial IRI is a complex event that involves various harmful mechanisms (e.g., production of reactive oxygen species and local increase in calcium ions) as well as inflammatory cells and signals like chemokines and cytokines. An involvement of platelets in the inflammatory reaction associated with IRI was discovered several years ago, but the underlying mechanisms are not yet fully understood. This mini review focusses on platelet contributions to the intricate picture of myocardial IRI. We summarize how upregulation of platelet surface receptors and release of immunomodulatory mediators lead to aggravation of myocardial IRI and subsequent cardiac damage by different mechanisms such as recruitment and activation of immune cells or modification of the cardiac vascular endothelium. In addition, evidence for cardioprotective roles of distinct platelet factors during IRI will be discussed.

show abstract

Section: Leukocyte-platelet-interactions In Irimentioning

confidence: 99%

Platelet Contributions to Myocardial Ischemia/Reperfusion Injury

2019

View full text Add to dashboard Cite

show abstract

“…To eliminate the pro-thrombotic activity, it was decided to add the amino acid sequence RGD (Arg-Gly-Asp) to PHBSP. It is known that this motif has pronounced antiaggregant properties (Pytela et al 1986, Sheu et al 1995, Hung et al 2017. In parallel, the PGP motive (Pro-Gly-Pro) was added to a number of compounds to improve their pharmacokinetic characteristics.…”

Section: Resultsmentioning

confidence: 99%

Non-hematopoietic erythropoietin-derived peptides for atheroprotection and treatment of cardiovascular diseases

Belyaeva¹,

Stepenko²,

Lyubimov³

et al. 2020

RRP

View full text Add to dashboard Cite

Relevance: Cardiovascular diseases continue to be the leading cause of premature adult death. Lipid profile and atherogenesis: Dislipidaemia leads to subsequent lipid accumulation and migration of immunocompetent cells into the vessel intima. Macrophages accumulate cholesterol forming foam cells – the morphological substrate of atherosclerosis in its initial stage. Inflammation and atherogenesis: Pro-inflammatory factors provoke oxidative stress, vascular wall damage and foam cells formation. Endothelial and mitochondrial dysfunction in the development of atherosclerosis: Endothelial mitochondria are some of the organelles most sensitive to oxidative stress. Damaged mitochondria produce excess superoxide and H2O2, which are the main factors of intracellular damage, further increasing endothelial dysfunction. Short non-hematopoietic erythropoietin-based peptides as innovative atheroprotectors: Research in recent decades has shown that erythropoietin has a high cytoprotective activity, which is mainly associated with exposure to the mitochondrial link and has been confirmed in various experimental models. There is also a short-chain derivative, the 11-amino acid pyroglutamate helix B surface peptide (PHBSP), which selectively binds to the erythropoietin heterodymic receptor and reproduces its cytoprotective properties. This indicates the promising use of short-chain derivatives of erythropoietin for the treatment and prevention of atherosclerotic vascular injury. In the future, it is planned to study the PHBSP derivatives, the modification of which consists in adding RGD and PGP tripeptides with antiaggregant properties to the original 11-member peptide.

show abstract

“…Для устранения протромботической активности к P-αB могут быть добавлены аминокислотные последовательности Arg-Gly-Asp и Lys-Gly-Asp. Известно, что Arg-Gly-Asp и Lys-Gly-Asp обладают выраженными антиагрегантными свойствами [20][21][22]. В ряде отечественных работ также были выявлены антитромботические и антиагрегантные свойства другого вспомогательного аминокислотного трипептида Pro-Gly-Pro.…”

Section: Discussionunclassified

11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats.

Korokin

Солдатов

Титце

et al. 2020

Farm. farmakol. (Pâtigorsk)

View full text Add to dashboard Cite

The aim of the study was to test whether P-αB can be positioned as a preventing and treating agent for cardiovascular diseases.Materials and methods. The study was performed on sexually mature male Wistar rats. Endothelial dysfunction was modulated by a 7-days intraperitoneal administration of L-NAME at the dose of 2.5 mg/100 g. P-αB, or erythropoietin (EPO), was used for therapy at the dose of 2.5 µg/100 g × 3 times for 7 days, the total dose was 7.5 µg/100 g. The function of endothelium was estimated by an endothelium-dependent and endothelium-independent vasodilation. In addition, a histological assessment of the abdominal aortic wall state and the analysis of eNos, Tnf and Il-1β genes expression were performed. To estimate prothrombotic properties, P-αB and EPO were administered, at the doses of 2.5 and 5 µg/100 g (3 times a day for 7 days, the total doses were 7.5 µg/100 g and 15 µg/100 g, respectively) and on the 8th day, the time of ferric (III) chloride-induced carotid artery thrombosis was estimated.Results. Theresults of the functional tests for endothelium-dependent and endothelium-independent vasodilatation, as well as the histological picture of the aorta have evidenced that P-αB and EPO do not affect L-NAME-induced hypertension but improve the endothelium function. At the same time, P-αB shows a significantly higher endothelial-protective activity, reducing the coefficient of endothelial dysfunction from 5.1±0.15 to 2.72±0.12. In addition, P-αB has significantly increased the expression of eNos and reduced the expression level of Tnf and Il-1β mRNA genes. Carrying out Ferric (III) chloride-induced carotid artery thrombosis has revealed that P-αB (5 µg/100 g × 3 times a day for 7 days, total dose was 15 µg/100 g) has a lower but statistically significant prothrombotic activity than EPO.Conclusion. P-αB can be positioned as an atheroprotector because of its ability to prevent the death of endothelial cells, as well as to reduce remodeling and proinflammatory activation of the vascular wall. However, the prothrombotic properties of P-αB limit its use as a preventing and treating agent for atherosclerosis-associated diseases.

show abstract

Trimucrin, an Arg-Gly-Asp containing disintegrin, attenuates myocardial ischemia-reperfusion injury in murine by inhibiting platelet function

Cited by 11 publications

References 20 publications

Platelet Contributions to Myocardial Ischemia/Reperfusion Injury

Platelet Contributions to Myocardial Ischemia/Reperfusion Injury

Non-hematopoietic erythropoietin-derived peptides for atheroprotection and treatment of cardiovascular diseases

11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats.

Contact Info

Product

Resources

About