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

Seyed Soheil Saeedi Saravi; Nicole R Bonetti; Ana Vukolic; Daria Vdovenko; Pratintip Lee; Luca Liberale; Cristina Basso; Stefania Rizzo; Alexander Akhmedov; Thomas F Lüscher; Giovanni G Camici; Jürg H Beer

doi:10.1016/j.vph.2023.107175

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

Vascul Pharmacol. 2023 Jun:150:107175. doi: 10.1016/j.vph.2023.107175. Epub 2023 Apr 25.

Affiliations

¹ Center for Translational and Experimental Cardiology, Department of Cardiology, University Hospital Zurich, University of Zurich, 8952 Schlieren, Switzerland.
² Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland; Department of Internal Medicine, Cantonal Hospital Baden, 5404 Baden, Switzerland.
³ Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland.
⁴ First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
⁵ Cardiovascular Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy.
⁶ Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland; Royal Brompton and Harefield Hospitals, Imperial and Kings College, London, UK.
⁷ Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland; University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland; Department of Research and Education, University Hospital Zurich, Zurich, Switzerland.
⁸ Center for Molecular Cardiology, University of Zurich, 8952 Schlieren, Switzerland; Department of Internal Medicine, Cantonal Hospital Baden, 5404 Baden, Switzerland. Electronic address: hansjuerg.beer@ksb.ch.

PMID: 37105373
DOI: 10.1016/j.vph.2023.107175

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.

Keywords: Cardiovascular aging; Heart failure with preserved ejection fraction (HFpEF); Omega-3 fatty acid; α-Linolenic acid (ALA).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging
Animals
Diet
Fatty Acids
Fatty Acids, Omega-3* / pharmacology
Fibrosis
Heart Failure*
Inflammation
Mice
Mice, Inbred C57BL
Stroke Volume / physiology
Ventricular Dysfunction, Left* / prevention & control

Substances

Fatty Acids, Omega-3
Fatty Acids