Description
IntroductionHeart failure (HF) is associated with myocardial inflammation and increased cardiac macrophage presence, with roles in both injury and repair. Meldonium has shown cardioprotective effects in both experimental models and clinical settings. However, its impact on inflammatory signalling and immune cell remodelling in heart failure with preserved ejection fraction (HFpEF) remains poorly understood.
Methods
HFpEF was induced in male C57BL/6N mice through 16 weeks of a high-fat diet (HFD) combined with the hypertension-inducing agent L-NAME (0.5 g/L) in drinking water. Meldonium (200 mg/kg/day) was administered together with drinking water from week 9. At the end of treatment, cardiac function was assessed using echocardiography and invasive measurement of left ventricular pressure. After sacrifice, myocardial tissues were collected for qPCR analysis of inflammatory gene expression (TNFα, Il-1β, Il-6) and for quantification of tissue-resident macrophages, which were analysed by flow cytometry using antibodies against CD45-PerCP-Cy5.5, CD64-APC, MHCII-APC/Cy7, CCR2-BV421, and Ly6G-FITC.
Results
Echocardiographic analysis revealed normal systolic function across all groups. Mice receiving HFD and L-NAME developed left ventricular hypertrophy, which was further augmented by meldonium treatment. The HFpEF phenotype was characterized by elevated left ventricular end-diastolic pressure (8.1±1.4 mmHg), which was normalized by meldonium treatment (3.1±1.1 mmHg). qPCR analysis indicated mild inflammatory activation in the meldonium-treated group, with TNFα expression increased approximately 2-fold, Il-1β nearly 2-fold, and Il-6 by 4-fold. The proportion of immunoregulatory macrophages (MHCII^high CCR2^−) was higher in meldonium-treated mice (12%) compared with controls (4%) and untreated HFpEF mice (5%). Pro-inflammatory macrophages (MHCII^low CCR2^+) increased to 3.9% in the meldonium group versus 1.6% in controls.
Conclusions
Meldonium improved cardiac hemodynamic parameters in experimental HFpEF while simultaneously promoting myocardial inflammatory gene expression and macrophage subset remodelling. These results suggest that meldonium effects may result from coordinated metabolic and immune modulation.
| Period | 19 Mar 2026 |
|---|---|
| Event title | Baltic Flow Cytometry Society 2026 International Conference |
| Event type | Conference |
| Location | Riga, LatviaShow on map |
| Degree of Recognition | International |