Proteomic analysis of CKD-associated left ventricular hypertrophy

ABSTRACT: Left ventricular hypertrophy (LVH) is critical in chronic kidney disease (CKD), but its mechanisms remain unclear. This study employed multi-omics approaches, including RNA-seq and integrated metabolomics, to characterize metabolic alterations in cardiomyocytes (CM) of CKD mice, revealing enhanced glutaminolysis and impaired oxidative phosphorylation. We identified that glutaminase 1 (GLS1), the rate-limiting enzyme of glutaminolysis, is significantly upregulated and enzymatically activated in CM under CKD conditions. A multi-center cohort study confirmed that serum-induced GLS1 activity was associated with LV hypertrophic remodeling. Cardiomyocyte-specific deletion or pharmacological inhibition of GLS1 attenuated CKD-induced cardiac hypertrophy. Proteomic analysis revealed that multiple circulating proteins in the serum of CKD patients are associated with GLS1 enzymatic activity. Furthermore, phosphate (Pi), a representative uremic toxin, functions as a critical modulator of GLS1 activity and expression, compromising mitochondrial bioenergetics by promoting ammonia production and reducing mitochondrially encoded respiratory chain proteins. These integrated metabolic effects underscore the pivotal role of GLS1 in orchestrating myocardial energy reprogramming, thereby contributing to CKD-induced LVH.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

SUBMITTER: Linnan Bai  

LAB HEAD: Junnan Wu

PROVIDER: PXD077955 | Pride | 2026-09-30

REPOSITORIES: Pride