Diminished arachidonate 5-lipoxygenase perturbs phase separation and transcriptional response of Runx2 to reverse pathological ventricular remodeling.

ABSTRACT:

Background

Arachidonate 5-lipoxygenase (Alox5) belongs to a class of nonheme iron-containing dioxygenases involved in the catalysis of leukotriene biosynthesis. However, the effects of Alox5 itself on pathological cardiac remodeling and heart failure remain elusive.

Methods

The role of Alox5 in pathological cardiac remodeling was investigated by Alox5 genetic depletion, AAV9-mediated overexpression in cardiomyocytes, and a bone marrow (BM) transplantation approach. Neonatal rat cardiomyocytes were used to explore the effects of Alox5 in vitro. Molecular and signaling pathways were revealed by CUT &Tag, IP-MS, RNA sequencing and bioinformatic analyses.

Findings

Untargeted metabolomics showed that serum 5-HETE (a primary product of Alox5) levels were little changed in p

SUBMITTER: Xie S 

PROVIDER: S-EPMC9672960 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature