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June 25, 2021Journal of Pharmacological SciencesOpen Access

Effects of 17-AAG on the RIP1/RIP3/MLKL pathway during the development of heart failure following myocardial infarction in rats

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Why the study?

The relationship between the cardioprotective effects of the Hsp90 inhibitor 17-AAG and the activity of cardiac RIP1/RIP3/MLKL necrosome-associated proteins in the failing heart after myocardial infarction remained unclear.

Does 17-AAG improve cardiac function and attenuate the RIP1/RIP3/MLKL pathway in rats following myocardial infarction?

Population

Wistar rats with myocardial infarction induced by coronary artery ligation

Comparison

17-AAG treatment vs without Hsp90 inhibitor treatment

Design

Preclinical animal study

Follow-up

8 weeks

Authors

TMTetsuro MarunouchiTokyo University of Pharmacy and Life SciencesTITakumi ItoKyushu Dental UniversitySOSumika OndaTokyo University of Pharmacy and Life Sciences

Discussion

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Overview

17-AAG attenuates RIP1/RIP3/MLKL activation post-MI in rats; leaves open whether necroptosis inhibition improves human HF outcomes.

Structured PICO

Does 17-AAG improve cardiac function and attenuate the RIP1/RIP3/MLKL pathway in rats following myocardial infarction?

P
Population
Wistar rats with myocardial infarction induced by coronary artery ligation (CAL)
I
Intervention
17-AAG (Hsp90 inhibitor) injected from the 2nd to the 8th week after myocardial infarction
C
Comparator
Myocardial infarction without Hsp90 inhibitor treatment
O
Outcome
Cardiac dysfunction, hypertrophy, fibrosis, and expression/phosphorylation levels of RIP1, RIP3, and MLKL at the 8th week after CALsurrogate

The Hsp90 inhibitor 17-AAG improves cardiac function and reduces remodeling in a rat model of post-MI heart failure by attenuating the RIP1/RIP3/MLKL necroptotic pathway.

Cite This Study

Marunouchi et al. (2021) studied this question.

synapsesocial.com/papers/6a72d0ec93a4d5cf641ae336https://doi.org/10.1016/j.jphs.2021.06.009
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Also Consider

Synapse has enriched 2 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1mTORC1 inhibition attenuates necroptosis through RIP1 inhibition-mediated TFEB activation2019 · 76 citations
  2. 2Spotlight on 17‐ AAG as an Hsp90 inhibitor for molecular targeted cancer treatment2019 · 135 citations