Diabetes mellitus aggravates myocardial inflammation and oxidative stress in aortic stenosis: a mechanistic link to heart failure with preserved ejection fraction (HFpEF) features
Authors' conclusion
DM exacerbates inflammation and oxidative stress in AS patients, leading to impaired NO-sGC-cGMP-PKG signaling and increased cardiomyocyte Fpassive. These conditions are reminiscent of the pathophysiology of heart failure with preserved ejection fraction (HFpEF). These alterations can be ameliorated through anti-inflammatory and antioxidant therapies, indicating potential therapeutic strategies for diabetic patients suffering from AS.
Study context
- Population
- Patients with aortic stenosis (AS); left ventricular myocardial biopsies
- Participants
- 28 LV myocardial biopsies
- Comparison
- Diabetic AS vs non-diabetic AS
- Diabetic ASn = 11
- Non-diabetic ASn = 17reference
- Outcome
- Myocardial inflammation, oxidative stress and cardiomyocyte function in diabetic vs non-diabetic AS
Main finding
As reported in the abstract
- Significantly elevated pro-inflammatory mediators (HMGB1, calprotectin) and inflammatory receptors (TLR2, TLR4, receptor for advanced glycation endproducts (RAGE)) in diabetic AS
- Enhanced NLRP3 inflammasome and release of IL-1, IL-6 and IL-18 in diabetic AS
- Increased oxidative stress markers (H2O2, 3-nitrotyrosine, lipid peroxidation (LPO), GSSG/GSH ratio) in myocardium and mitochondria in diabetic AS
- Impaired nitric oxide (NO)-sGC-cGMP-PKG signalling, decreased titin phosphorylation and increased cardiomyocyte passive stiffness (Fpassive) in diabetic AS
- In vitro IL-6 inhibitor and GSH normalised the elevated Fpassive in diabetic AS to levels comparable to the non-diabetic group
- In vitro protein kinase G (PKG) and the SGLT2 inhibitor empagliflozin reduced Fpassive in diabetic AS cardiomyocytes, though not to non-diabetic levels
Original publication
Diabetes mellitus aggravates myocardial inflammation and oxidative stress in aortic stenosis: a mechanistic link to HFpEF features. Cardiovasc Diabetol. Published 13 May 2025. doi:10.
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