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Long-term dietary n3 fatty acid prevents aging-related cardiac diastolic and vascular dysfunction

Saeedi Saravi, Seyed Soheil; Bonetti, Nicole R; Vukolic, Ana; Vdovenko, Daria; Lee, Pratintip; Liberale, Luca; Basso, Cristina; Rizzo, Stefania; Akhmedov, Alexander; Lüscher, Thomas F; Camici, Giovanni G; Beer, Jürg H (2023). Long-term dietary n3 fatty acid prevents aging-related cardiac diastolic and vascular dysfunction. Vascular Pharmacology, 150:107175.

Abstract

Aims: The prevalence of left ventricular (LV) diastolic and vascular dysfunction increases with age, eventually leading to heart failure with preserved ejection fraction (HFpEF). A preventive strategy is an unmet medical need. We and others reported previously on the beneficial effects of omega-3 fatty acid alpha linolenic acid (ALA) on cardiovascular disorders in animal models and translational studies. We now investigate whether long-term dietary ALA could prevent LV diastolic dysfunction and vascular aging in a murine model.

Methods and results: Wild-type C57BL/6 J mice were fed a chow or ALA diet for 12 months, starting at 6 months of age. Here, we show that aged (~18 months) mice recapitulate major hallmarks of HFpEF, including LV diastolic dysfunction with preserved ejection fraction, impaired vascular function, cardiac fibrosis, arterial stiffening and inflammation, as well as elevated B-type natriuretic peptide (BNP). Long-term ALA supplementation upregulated the mitochondrial tricarboxylic acid enzyme Idh2 and the antioxidant enzymes SOD1 and Gpx1. It also has been associated with reduced inflammation and ECM remodeling, accompanied by a significant downregulation of fibrosis biomarkers MMP-2 and TGF-β in both cardiac and vascular tissues obtained from aged mice. Our data exhibited the preventive effects of dietary ALA against LV diastolic dysfunction, impaired vasorelaxation, cardiac fibrosis, inflammation and arterial stiffening in aged mice.

Conclusions: We provide evidence and a simplified mechanistic insight on how long-term ALA supplementation is a successful strategy to prevent the development of age-related diastolic and vascular dysfunction.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Molecular Cardiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
Dewey Decimal Classification:610 Medicine & health
570 Life sciences; biology
Scopus Subject Areas:Life Sciences > Physiology
Life Sciences > Molecular Medicine
Life Sciences > Pharmacology
Uncontrolled Keywords:Pharmacology, Molecular Medicine, Physiology
Language:English
Date:June 2023
Deposited On:24 Jan 2024 09:18
Last Modified:30 Oct 2024 02:41
Publisher:Elsevier
ISSN:1537-1891
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.vph.2023.107175
PubMed ID:37105373
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  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

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