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TCRC Seminar with Dr. Timothy O'Connell on May 11

This Translational Cardiovascular Research Center (TCRC) monthly seminar series will feature Dr. Timothy O'Connell from the University of Minnesota School of Medicine. This event will be hybrid (virtual and in-person).

When: Wednesday, May 11, 2022 from 12-1 p.m.

Where: Virtual via Zoom and in-person at the Health Science Education Building, Room C206, 435 N. 5th Street, Phoenix, AZ

Invited speaker:
Timothy O'Connell, PhD, associate professor, Department of Integrative Biology and Physiology, University of Minnesota School of Medicine
Seminar title: "Ffar4 regulates cardiac oxylipin balance to resolve inflammation and attenuate HFpEF"

Christopher Glembotski, PhD, professor of internal medicine and director, TCRC, University of Arizona College of Medicine – Phoenix
Shirin Doroudgar, PhD, assistant professor of internal medicine and inaugural member, TCRC, University of Arizona College of Medicine – Phoenix


Heart failure preserved ejection fraction (HFpEF) is a complex clinical syndrome, but a predominant subset of patients have metabolic syndrome (MetS). Mechanistically, systemic, non-resolving inflammation associated with MetS might promote HFpEF. Free fatty acid receptor 4 (Ffar4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that improves metabolism and attenuates inflammation. Therefore, we hypothesized Ffar4 would attenuate remodeling in HFpEF secondary to MetS (HFpEF-MetS). To test this, mice with systemic deletion of Ffar4 (Ffar4KO) were fed a high-fat/high-sucrose diet with L-NAME to induce HFpEF-MetS. In male Ffar4KO mice, this HFpEF-MetS diet-induced similar metabolic deficits, but worsened diastolic function and microvascular rarefaction. Conversely, in female Ffar4KO mice, the diet produced greater obesity but no worsened ventricular remodeling. In males, loss of Ffar4 altered the balance of inflammatory oxylipins in the heart, decreasing the eicosapentaenoic acid-derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE), while increasing the arachadonic acid-derived, proinflammatory oxylipin 12-hydroxyeicosatetraenoic acid (12-HETE). This increased 12-HETE/18-HEPE ratio reflected a more pro-inflammatory state and was associated with increased macrophage numbers, which in turn correlated with worsened ventricular remodeling in male Ffar4KO hearts. In summary, our data suggest that Ffar4 controls the proinflammatory/pro-resolving oxylipin balance in the heart to resolve inflammation and attenuate HFpEF remodeling.


Faculty, Staff, Students, Alumni, Community
University of Arizona Health Sciences, College of Medicine – Phoenix


Tina Allen
College of Medicine – Phoenix
Translational Cardiovascular Research Center