Dysregulated inflammation, oxidative stress, and protein quality control in diabetic heart failure with preserved ejection fraction (HFpEF): unraveling mechanisms and therapeutic targets
Authors' conclusion
The findings of this study elucidate a mechanistic relationship among diabetes, inflammation, oxidative stress, and PQC impairment in the context of HFpEF. Therapeutic strategies that target these dysregulated pathways, including IL-6 inhibition, mitochondrial antioxidants, and chaperone-mediated protection, may enhance myocardial function in HFpEF patients with T2DM. Addressing these molecular dysfunctions could facilitate the development of novel interventions specifically tailored to the diabetic HFpEF population.
Study context
- Population
- LV myocardial tissue from HFpEF patients with and without diabetes
- Comparison
- Diabetic vs non-diabetic HFpEF myocardium
- Outcome
- Myocardial inflammation, oxidative stress, signalling and protein quality control (PQC) in diabetic HFpEF
Main finding
As reported in the abstract
- Significantly heightened inflammation in diabetic HFpEF hearts, with upregulation of NF-κB, IL-6 and the NLRP3 inflammasome
- Elevated oxidative stress, diminished nitric oxide (NO) bioavailability and impaired NO-sGC-cGMP-PKG activation
- Dysregulated insulin signalling: decreased AKT phosphorylation and impaired AMPK/mTOR-mediated autophagy regulation
- Reduced HSP27 and HSP70 expression, correlated with increased cardiomyocyte passive stiffness
- IL-6 inhibition, Mito-TEMPO and HSP administration reduced Fpassive and improved cardiomyocyte mechanical properties
Original publication
Dysregulated inflammation, oxidative stress, and protein quality control in diabetic HFpEF: unraveling mechanisms and therapeutic targets. Cardiovasc Diabetol. Published 14 May 2025. doi:10.
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