Non-coding RNAs in the pathophysiology of heart failure with preserved ejection fraction

Jalink, Elisabeth A.; Schonk, Amber W.; Boon, Reinier A.; Juni, Rio P.

doi:10.3389/fcvm.2023.1300375

Cited by 3 publications

(1 citation statement)

References 250 publications

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“…MiRNAs control expression of over 60% of protein coding genes, highlighting their impact on cell physiology. Several miRNA-based therapies are under development in the field of cardiovascular disease ( 15 ). Specific miRNAs can potentially be used as biomarkers for noncommunicable diseases ( 16 – 18 ).…”

Section: Introductionmentioning

confidence: 99%

Divergent cardiac and renal effects of miR-181c-5p inhibition in a rodent heart failure model

Boen,

Gevaert,

Dendooven

et al. 2024

Front. Cardiovasc. Med.

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AimsMiR-181c-5p overexpression associates with heart failure (HF) and cardiac damage, but the underlying pathophysiology remains unclear. This study investigated the effect of miR-181c-5p inhibition on cardiac function and fibrosis in a rodent model of diastolic dysfunction, and evaluated additional effects on kidney as relevant comorbid organ.Methods and resultsDiastolic dysfunction was induced in male C57/BL6J mice (n = 20) by combining high-fat diet, L-NG-nitroarginine methyl ester, and angiotensin II administration, and was compared to sham controls (n = 18). Mice were randomized to subcutaneous miR-181c-5p antagomiR (INH) or scrambled antagomiR injections (40 mg/kg/week). HF mice demonstrated diastolic dysfunction and increased fibrosis, which was attenuated by INH treatment. Remarkably, HF + INH animals had a threefold higher mortality rate (60%) compared to HF controls (20%). Histological examination revealed increased glomerular damage in all INH treated mice, and signs of thrombotic microangiopathy (TMA) in mice who died prematurely. Quantitative polymerase chain reaction demonstrated a miR-181c-5p-related downregulation of cardiac but not renal Tgfbr1 in HF + INH mice, while INH treatment reduced renal but not cardiac Vegfa expression in all mice.ConclusionThis study demonstrates cardiac anti-fibrotic effects of miR-181c-5p inhibition in a rodent HF model through targeting of Tgfbr1 in the heart. Despite improved diastolic function, HF + INH mice had higher mortality due to increased predisposition for TMA, increased renal fibrosis and glomerular damage, associated with Vegfa downregulation in kidneys.

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Section: Introductionmentioning

confidence: 99%

Divergent cardiac and renal effects of miR-181c-5p inhibition in a rodent heart failure model

Boen,

Gevaert,

Dendooven

et al. 2024

Front. Cardiovasc. Med.

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Nrf2-Keap1 in Cardiovascular Disease: Which Is the Cart and Which the Horse?

Dhyani,

Tian,

Gao

et al. 2024

Physiology

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High levels of oxidant stress in the form of reactive oxidant species (ROS) are prevalent in the circulation and tissues in various types of cardiovascular disease including heart failure, hypertension, peripheral arterial disease, and stroke. Here we review the role of nuclear factor erythroid 2-related factor 2 (Nrf2), an important and widespread antioxidant and anti-inflammatory transcription factor that may contribute to the pathogenesis and maintenance of cardiovascular diseases. We review studies showing that downregulation of Nrf2 exacerbates heart failure, hypertension and autonomic function. Finally, we discuss the potential for using Nrf2 modulation as a therapeutic strategy for cardiovascular diseases and autonomic dysfunction.

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Plasma and Myocardial miRNomes Similarities and Differences during Cardiac Remodelling and Reverse Remodelling in a Murine Model of Heart Failure with Preserved Ejection Fraction

Thibodeau,

Labbé,

Walsh-Wilkinson

et al. 2024

Biomolecules

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Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterised by multiple risk factors touching various organs outside the heart. Using a murine HFpEF model, we studied cardiac reverse remodelling (RR) after stopping the causing metabolic-hypertensive stress (MHS; Angiotensin II [AngII] and a high-fat diet [HFD]) after 28 days and introducing voluntary exercise (VE) for four more weeks. We measured the effects of MHS and RR on the plasma and myocardial microRNA (miR) profile (miRNome) to characterise better cardiac and non-cardiac responses to HFpEF-inducing risk factors and their reversibility. AngII alone, the HFD or the MHS caused cardiac hypertrophy (CH), left ventricular (LV) concentric remodelling and left atrial enlargement in females. Only AngII and the MHS, but not HFD, did in males. After RR, CH, LV concentric remodelling and atrial enlargement were normalised. Among the 25 most abundant circulating miRs, 10 were modulated by MHS. Plasma miRNomes from AngII, HFD or MHS mice shared 31 common significantly modulated miRs (24 upregulated and 7 downregulated), suggesting that the response of organs producing the bulk of those circulating miRs was similar even for seemingly different stress. In the LV, 19 out of 25 most expressed miRs were modulated. RR restored normality for the plasma miRNome but not for the LV miRNome, which remained mostly unchanged. Our results suggest that abnormalities persist in the myocardium of the HFpEF mice and that the normalisation of circulatory markers may be falsely reassuring after recovery.

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Non-coding RNAs in the pathophysiology of heart failure with preserved ejection fraction

Cited by 3 publications

References 250 publications

Divergent cardiac and renal effects of miR-181c-5p inhibition in a rodent heart failure model

Divergent cardiac and renal effects of miR-181c-5p inhibition in a rodent heart failure model

Nrf2-Keap1 in Cardiovascular Disease: Which Is the Cart and Which the Horse?

Plasma and Myocardial miRNomes Similarities and Differences during Cardiac Remodelling and Reverse Remodelling in a Murine Model of Heart Failure with Preserved Ejection Fraction

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