The sulphydryl containing ACE inhibitor Zofenoprilat protects coronary endothelium from Doxorubicin-induced apoptosis

Monti, Martina; Terzuoli, Erika; Ziche, Marina; Morbidelli, Lucia

doi:10.1016/j.phrs.2013.08.003

Cited by 36 publications

(35 citation statements)

References 35 publications

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“…ADR lead to activate proapoptotic signaling pathways through p53 activation (Monti et al 2013). Furthermore, ADR was reported to impair progenitor cell renewal/cardiac repair as well (Shi et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Acute adriamycin-induced cardiotoxicity is exacerbated by angiotension II

et al. 2014

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Adriamycin (ADR) increases the production of reactive oxygen species (ROS), which diminishes mitochondrial function. Angiotensin-II stimulates mitochondrial ROS generation. The aim of the study was to examine whether angiotensin converting enzyme (ACE) or renin inhibitors protect against ADR-induced mitochondrial function impairment. Rats were divided into five groups as control, ADR, co-treatment ADR with captopril, co-treatment ADR with aliskiren, co-treatment ADR with both captopril and aliskiren. Left ventricular function and blood pressures were assessed at the end of treatment period. Mitochondrial membrane potential (MMP) and ATP levels were determined. ADR treatment decreased the left ventricular pressure and increased the left ventricular end-diastolic pressure. ADR decreased MMP and ATP levels in myocyte mitochondria due to increasing oxidative stress. ADR decreased MMP and ATP levels due to increased oxidative stress in the heart. Inhibitors of ACE and renin caused the elevation of the decreased of MMP and ATP levels. The pathologic changes in electrocardiogram, blood pressure and left ventricular function were decreased by inhibition of Ang-II production. We concluded that inhibitors of angiotensin II are effective against ADR cardiotoxicity via the restoration of MMP and ATP production and prevention of mitochondrial damage in vivo.

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Section: Introductionmentioning

confidence: 99%

Acute adriamycin-induced cardiotoxicity is exacerbated by angiotension II

et al. 2014

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“…Moreover, a protective effect by H 2 S on doxorubicin induced cardiotoxicity has been recently reported [86]. We have demonstrated that H 2 S mediates zofenoprilat activity, since cystathionine γ-lyase (CSE) is upregulated by the drug and CSE pharmacological inhibition prevents zofenoprilat protective effects on doxorubicin induced damage both at a molecular (p53, caspase-3) and a functional level (cell survival) [78] (Fig. 2).…”

Section: Aceimentioning

confidence: 59%

“…The previously described prosurvival signaling pathway (activation of PI-3K dependent eNOS and upregulation of endogenous FGF-2 and telomease reverse transcriptase TERT) [77] was not involved in the protective effect of doxorubicin induced damage, which, instead, could be ascribed to cystathionine gamma lyase (CSE) dependent availability of H 2 S from zofenoprilat. Indeed the levels of CSE protein were upregulated by zofenoprilat treatment (10 μM, 4 h) [78] ( Fig. 3).…”

Section: Nitric Oxide Donorsmentioning

confidence: 87%

“…We have recently reported that ACEi dependent H 2 S exerts protective activity on ECs through activation of K ATP channel, PI-3 K and eNOS, as well as up-regulation of FGF-2 and telomerase, thus maintaining endothelial longevity and function [76][77][78]104] (Fig. 4).…”

Section: Nitric Oxide Donorsmentioning

confidence: 99%

“…In microvascular endothelium, zofenoprilat up-regulates eNOS, FGF-2 and telomerase (TERT) mRNA, inducing cell survival, rescuing damaged ECs and promoting physiological angiogenesis without synergistic effects with known angiogenic factors produced by tumors as VEGF [76,77]. Recently, we reported the protective properties of zofenoprilat, known to have an elevated tropism for the heart, against doxorubicin-induced toxicity in coronary ECs [78]. The ACEi zofenoprilat preserves coronary EC survival and function damaged by doxorubicin, and appears to exert its protective effects owing to its SH group, besides the ACE inhibitory function [79].…”

Section: Aceimentioning

confidence: 99%

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