Dear Colleagues, 

Wednesday, February 9^th, at 12:00, Emma Börgeson and Stephan Lange will present their research in the Biomedicine Seminar Series.

Therapeutic potential of pro-resolving lipids in cardiometabolic disease

Low-grade chronic inflammation is a hallmark and driver of cardiometabolic disease. Enhancing the endogenous mechanisms that promote the resolution of inflammation through administration of lipoxins, a group of specialized pro-resolving lipid mediators, has been suggested as a novel therapeutic strategy to reduce inflammation and attenuate disease.

We have demonstrated that the lipoxin family attenuate obesity-related experimental cardiometabolic disease in rodents by promoting inflammatory resolution. We now perform ex vivo studies to investigate if the same proof-of-principle applies to human tissues, and study the underlying molecular mechanisms involved. Intriguingly, lipoxin-mediated effects are distinctly different in healthy individuals versus patients. This finding demonstrates that therapeutic applications using pro-resolving lipids may need to be tailored to the individual through a personalized medicine approach. Ongoing experiments centre around the clinical and molecular characterization of patients and the hypothesis that cardiometabolic health/disease is, at least in part, determined by an individual’s endogenous capability to resolve inflammation.

Our studies involve an array of cutting edge methodologies that study resolution-mediated actions on the molecular and cellular level, including translational ex vivo models of inflammation, detailed FACS profiling, lipidomics and proteome analyses, next-generation sequencing, and computational bioinformatics of clinical datasets. When focussing on translating basic science to clinical research, we utilize a number of clinical cohorts that help us investigate the pathophysiology of cardiometabolic disease. For more information and as a resource for potential collaborations, please see: https://www.borgesonlab.org/clinical-cohorts.html. 

Diastolic dysfunction and HFpEF: from obscurity into the limelight

Muscle proteins of the obscurin protein family were shown to play roles for sarcomere organization, sarcoplasmic reticulum (SR) and sarcolemma architecture and function. However, their precise biological roles and involvement in cardiomyopathies remain to be fully understood.
We studied cardiac roles for obscurin and its close homologue obscurin-like 1 (Obsl1). Mice lacking obscurin and Obsl1 develop normally, but show dramatic changes to SR-architecture and function on the microscopic and proteome level. While obscurin has been shown to be important for SR-structure, our data reveal for the first time that Obsl1 has similar functions. Alterations to SR-structure are also reflected in dramatically reduced SR-volume and calcium cycling. While systolic functions are near normal on the physiological level in controls, loss of obscurin/Obsl1 results in a profound cardiac relaxation defect in double knockout mice only, reflected by increased Tau and Min dP/dT-values from our hemodynamics analyses. Intriguingly, the diastolic dysfunction is not accompanied by hypertrophy or increased fibrosis, but heart-failure specific changes on the metabolic level.

Taken together, our data indicate that obscurin and Obsl1 are crucial for SR-structure, calcium storage and re-uptake as well as mitochondrial structure and function. We propose that obscurin/Obsl1 double-knockout mice may serve as a new model to investigate age-dependent diastolic dysfunction and HFpEF.

For more information on our projects and potential collaborations, please visit: http://slangelab.org/

Venue:

The seminar will be held at 12:00 pm in 1162-013 in Auditorium A

And at Zoom: 

https://aarhusuniversity.zoom.us/j/62758258306?pwd=WUt2N25ia3ZSdXhoZUlLNzcvR0hkUT09

The talks are 2x25 minutes followed by 5 minutes of discussion, for a total of 1 hr.

Sign-up: 

It is possible to sign-up for a free sandwich if you follow this link: https://events.au.dk/biomedicineseminar9february2022

Please note the deadline for sandwich sign-up is Monday the 7^th of January.

Biomedicine seminar organizing committee:

Mikkel Vendelbo

Line Reinert

Søren Egedal Degn 

Martin Kristian Thomsen