Thomas F. Lüscher (United Kingdom)
Royal Brompton and Harefield Hospitals and Imperial College Royal Brompton and Harefield Hospitals and Imperial CollegeAuthor Of 2 Presentations
Atherosclerosis management: will the future look smarter? (ID 1330)
O037 - Dietary omega-3 fatty acid reverses age-linked heart failure with preserved ejection fraction (ID 158)
Abstract
Background and Aims
Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in aged adults, yet no optimal pharmacological therapy has emerged for improved outcomel in HFpEF. Therefore, there is an urgent need for novel effective interventions in the age‐related HFpEF. The plant-derived omega-3-fatty-acid α-linolenic-acid (ALA) has emerged to confer potential protective effects in cardiovascular disease. Our recent findings reveal that lifelong dietary ALA dampens thrombotic and cerebrovascular events in aged mice. The purpose of this study was to elucidate the reversal of age-related HFpEF phenotype by long-term nutritional ALA supplementation.
Methods
6-month-old (young) wild-type C57BL/6J mice were fed a low, as control, or high ALA diet for more than 12 months. Here, we show that aged (>18 months) mice on low ALA diet recapitulate major hallmarks of HFpEF, including diastolic dysfunction with preserved left ventricular ejection fraction, cardiac interstitial fibrosis, impaired acetylcholine-induced relaxation of aortic segments, and arterial stiffness.
Results
Intriguingly, we revealed that long-term ALA-rich diet reverses diastolic dysfunction, vascular relaxation capacity, reduced pulse wave velocity, interstitial cardiac fibrosis, and coincident hemodynamic abnormalities in aged mice. These findings are accompanied by blunting of inflammatory responses and a remarkable reduction in the expression of matrix-metalloproteinase-2 (MMP-2) by high ALA diet.
Conclusions
Our results demonstrate previously unrecognized protective effects of dietary ALA against impaired cardiovascular functional outcomes and cardiac structural changes typical of HFpEF in aged mice. Taken together, these data support the ALA-based nutritional intervention as a safe, plant derived and easily accessible therapeutic strategy for age-related HFpEF.