Programmed Cell Death in the Left and Right Ventricle of the Late Phase of Post-Infarction Heart Failure

0535047 - FGÚ 2021 RIV CH eng J - Journal Article
Lichý, M. - Szobi, A. - Hrdlička, Jaroslav - Neckář, Jan - Kolář, František - Adameová, A.
Programmed Cell Death in the Left and Right Ventricle of the Late Phase of Post-Infarction Heart Failure.
International Journal of Molecular Sciences. Roč. 21, č. 20 (2020), č. článku 7782. E-ISSN 1422-0067
R&D Projects: GA MZd(CZ) NV15-27735A
Institutional support: RVO:67985823
Keywords : heart failure * cell death * autophagy * necroptosis
OECD category: Biochemistry and molecular biology
Impact factor: 5.924, year: 2020
Method of publishing: Open access
https://www.mdpi.com/1422-0067/21/20/7782

While necroptosis has been shown to contribute to the pathogenesis of post-infarction heart failure (HF), the role of autophagy remains unclear. Likewise, linkage between these two cell death modalities has not been sufficiently investigated. HF was induced by 60-min left coronary occlusion in adult Wistar rats and heart function was assessed 6 weeks later followed by immunoblotting analysis of necroptotic and autophagic proteins in both the left (LV) and right ventricle (RV). HF had no effect on RIP1 and RIP3 expression. PhosphoSer229-RIP3, acting as a pro-necroptotic signal, was increased in LV while deceased in RV of failing hearts. Total MLKL was elevated in RV only. Decrease in pSer555-ULK1, increase in pSer473-Akt and no significant elevation in beclin-1 and LC3-II/I ratio indicated rather a lowered rate of autophagy in LV. No beclin-1 upregulation and decreased LC3 processing also suggested the inhibition of both autophagosome formation and maturation in RV of failing hearts. In contrast, p89 PARP1 fragment, a marker of executed apoptosis, was increased in RV only. This is the first study showing a different signaling in ventricles of the late phase of post-infarction HF, highlighting necroptosis itself rather than its linkage with autophagy in LV, and apoptosis in RV.
Permanent Link: http://hdl.handle.net/11104/0313152