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LHI Lecture: Timothy D. O'Connell, PhD

The Lillehei Heart Institute
Event organized by The Lillehei Heart Institute

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“EPA-Ffar4 Cardioprotective Signaling: Implications for HFpEF”

Timothy D. O’Connell, Ph.D.
Assistant Professor, Department of Integrative Biology and Physiology (IBP)
Assistant Professor, Department of Pharmacology
University of Minnesota

More about Dr. O’Connell from IBP website:

1-125 Cancer & Cardiovascular Research Building (CCRB)
2231 6th St SE
UM Biodiscovery District
Map: http://www1.umn.edu/twincities/maps/CCRB/
***The lecture will be simulcast via videoconference in 299 VCRC (401 E River Parkway)***

Bring your lunch, Beverages will be provided.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs) reduce sudden death in coronary heart disease, and we are investigating whether ω3-PUFAs show a benefit in heart failure. However, the use of ω3-PUFAs in cardiovascular disease is controversial, and questions of mechanism and efficacy remain. Our studies indicate that eicosapentaenoic acid (EPA, an ω3-PUFA) prevents interstitial fibrosis and pathologic remodeling in the transverse aortic constriction (TAC) model of pressure overload induced heart failure in mice. However, EPA supplementation does not lead to incorporation into cardiac myocytes or fibroblasts in vivo, a traditional mechanism of action. Interestingly, our results show that free fatty acid receptor 4 (Ffar4), a G-protein coupled receptor for long-chain fatty acids, is expressed in cardiac myocytes and fibroblasts. In primary cultures of cardiac fibroblasts, Ffar4 is sufficient and required to prevent TGFβ1-induced fibrosis, suggesting Ffar4 might mediate EPA cardioprotection, and identifying an entirely novel mechanism of action. Furthermore, our results indicate that EPA-mediated cardioprotection is concentration-dependent. Interestingly, parallel results are observed in an analysis of clinical trials with ω3-PUFAs in cardiovascular disease, which suggest a concentration dependency for efficacy. In summary, our findings identify EPA-Ffar4 signaling as a novel cardioprotective mechanism, and suggest that EPA-mediated cardioprotection is concentration-dependent.