The Effects of AEB071 (Sotrastaurin) with Tacrolimus on Rat Heterotopic Cardiac Allograft Rejection and Survival

Fang, Y.H.; Joo, Dong Jin; Lim, Beom Jin; Huh, Kyu Ha; Kim, Myoung Soo; Suh, Hwal; Kim, Yu Seun

doi:10.1016/j.jss.2011.06.039

Cited by 7 publications

(5 citation statements)

References 29 publications

(39 reference statements)

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“…These data are comparable to results reported by others [22,23,24]. Nevertheless, transplantation of hamster hearts to non-sensitised rat recipients in the semi-discordant setting is in fact a relevant model for xenotransplantation studies, as the survival times are significantly lower when compared to allogeneic rat-to-rat transplantation, which are reported to be around 20 days, depending on the strain combination [25,26]. …”

Section: Discussionsupporting

confidence: 89%

The Coronary Microcirculation in Hamster-to-Rat Cardiac Xenografts

Geiger

Buchholz²,

Michel³

et al. 2015

Eur Surg Res

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Background: The aim of this study was to establish a new experimental model to directly analyse the coronary microcirculation in cardiac xenografts. Methods: Intravital fluorescence microscopy (IVM) of the subepicardial microcirculation in heterotopically transplanted hamster-to-rat cardiac xenografts was performed at 30 and 90 min of reperfusion. We quantitatively assessed the microcirculatory perfusion characteristics as well as the interactions of leukocytes and platelets with the endothelium of postcapillary coronary venules in non-sensitised as well as sensitised recipients. Results: In this first experimental IVM study of cardiac xenografts, we successfully visualised the subepicardial microcirculation, i.e. feeding arterioles, nutritive capillaries and draining postcapillary venules, during reperfusion. Leukocyte-endothelial and platelet-endothelial cell interactions could be quantified. In the non-sensitised group, the myocardial microcirculation remained stable during the observation period of 90 min, whereas in the sensitised group, xenografts were rejected immediately. Conclusions: We established a model for the assessment of the microcirculatory dysfunction and inflammation during ischaemia/reperfusion injury in hamster-to-rat cardiac xenografts.

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Section: Discussionsupporting

confidence: 89%

The Coronary Microcirculation in Hamster-to-Rat Cardiac Xenografts

Geiger

Buchholz²,

Michel³

et al. 2015

Eur Surg Res

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“…Another example of a pan-PKC inhibitor that shows some selectivity for PKCθ is sotrastaurin (AEB071). Several animal studies used this inhibitor as immunosuppressive drug during heart transplantation, resulting in lower transplant rejection and increased survival rates [145,146]. Sotrastaurin was used in several clinical trials, mostly as immunosuppressive after organ transplantation or to treat various cancer types.…”

Section: Inhibiting Novel Pkcs In Heart Disease and After Heart Transmentioning

confidence: 99%

PKC and PKN in heart disease

Marrocco

Bogomolovas

Ehler³

et al. 2019

Journal of Molecular and Cellular Cardiology

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The protein kinase C (PKC) and closely related protein kinase N (PKN) families of serine/threonine protein kinases play crucial cellular roles. Both kinases belong to the AGC subfamily of protein kinases that also include the cAMP dependent protein kinase (PKA), protein kinase B (PKB/AKT), protein kinase G (PKG) and the ribosomal protein S6 kinase (S6K). Involvement of PKC family members in heart disease has been well documented over the years, as their activity and levels are mis-regulated in several pathological heart conditions, such as ischemia, diabetic cardiomyopathy, as well as hypertrophic or dilated cardiomyopathy. This review focuses on the regulation of PKCs and PKNs in different pathological heart conditions and on the influences that PKC/PKN activation has on several physiological processes. In addition, we discuss mechanisms by which PKCs and the closely related PKNs are activated and turned-off in hearts, how they regulate cardiac specific downstream targets and pathways, and how their inhibition by small molecules is explored as new therapeutic target to treat cardiomyopathies and heart failure.

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“…Rats were randomly divided into 4 groups (n=10 per group): the Control group, in which control rats were treated with 0.9% NS orally; the EAMG group, in which EAMG rats were treated with 0.9% NS orally; the AEB-071+EAMG group, which received 30 mg/kg AEB-071 per day by gavage 15 days after EAMG immunization in accordance with previous studies [ 14 , 16 ]; and the AZP+EAMG group, which received the AZP (25 mg/kg) per day orally 15 days after EAMG immunization. The concentration of AEB071 was based on previous experiments [ 21 ]. The AZP manual recommends a concentration of 1–3 mg/kg, which was calculated based on the conversion ratio from human to animal dosage.…”

Section: Methodsmentioning

confidence: 99%