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Team Per Eriksson

Research focus

Molecular pathology of aortic aneurysm, allele-specific gene expression.

Introduction

The long-term interest of the Eriksson team is to investigate the underlying molecular mechanism of aortic aneurysm development. Aortic aneurysm is a silent disease and the first manifestation is often aortic dissection or aortic rupture, both lethal conditions unless surgery is performed acutely. Our studies aim at gaining insights regarding the clinical course and predictors of outcome in aortic aneurysm, to identify biomarkers for the disease and to elucidate the etiologies and pathogenic mechanisms.

Major research focus

We have previously shown that being born with a bicuspid (BAV) instead of the normal tricuspid (TAV) aortic valve is a major risk factor for developing aneurysm in the ascending aorta. BAV is, by far, the most common congenital heart disorder, and is present in 1-2% of the population.

Currently, two major hypotheses have been proposed to explain the more fragile aorta in BAV patients. The first is that a developmental abnormality or a genetic predisposition in BAV results in structural weakness of the aorta, which renders it more susceptible to aortic complications. The second or ‘’hemodynamic’’ theory argues that the chronic exposure of ascending aortic wall to higher blood flow velocities and eccentric flow jets due to the geometry of a BAV lead to a higher propensity of the BAV aorta to aorthopathy.

A unique clinical cohort is the basis for our research. Our biobank includes at present >1800 patients undergoing valve replacement and/or repair of the ascending aorta. Today our cohort is one of the largest and most comprehensive in the world. The extensive biobank consists of DNA, plasma, serum, and vascular tissue biopsies from all patients. Uniquely, we have collected biopsies from multiple tissues from the same individual of the first 600 patients (ascending aorta, internal thoracic artery, heart, and liver). Furthermore, smooth muscle cells and endothelial cells from ascending aortas of BAV and TAV patients have been isolated. Besides inherited properties, we study the possible dysregulation of biological pathways due to abnormal hemodynamic stress, which may contribute and/or lay the foundation for more fragility in BAV aorta. In order to do so, we integrate the core molecular biology with genomic, genetic and bioinformatics analysis. Candidate genes and pathways are initially identified by transcriptomics, proteomics, epigenomics and genetic analyses. Functional evaluations are performed using cell culture and in vitro analyses. RNA sequencing is used to study allele-specific gene expression.

Collaborations

The study on BAV associated aortopathy is a close collaboration with the group of Professor Anders Franco-Cereceda at the Cardiothoracic Surgery Unit at the Karolinska University Hospital Solna. Studies on abdominal aortic aneurysm are in collaborations with Docent Joy Roy and Professor Rebecka Hultgren at the Vascular Surgery group, Karolinska University Hospital Solna (http://ki.se/en/mmk/star-stockholm-aneurysm-research-group). We have been members of Leducq transatlantic network on BAV disease MIBAVA and the EU-financed network, FAD, Fighting Aneurysmal Disease. The studies are supported by the Swedish Research Council, the Swedish Heart-Lung Foundation and the Stockholm County Council.

Affiliated to the team is Lasse Folkersen, PhD, Sankt Hans Hospital Roskilde, Denmark, and Maria Sabater Lleal, PhD, senior researcher, Barcelona.

Team members

Per Eriksson PhD, Professor, Group Leader

Karin Lång Laboratory assistant

Jesper Gådin PhD, Post Doctoral Fellow

Hanna Björck PhD, Assistant Professor

Flore-Anne Poujade PhD, Post Doctoral Fellow

Otto Bergman PhD, Post Doctoral Fellow

Nancy Simon Laboratory Assistant

Anders Mälarstig PhD, Associated

Bamba Gaye PhD, Associated

Maxim Vignac Associated

Recent key publications

High-Resolution Regulatory Maps Connect Vascular Risk Variants to Disease-Related Pathways.
Åkerborg �, Spalinskas R, Pradhananga S, Anil A, Höjer P, Poujade F, et al
Circ Genom Precis Med 2019 Mar;12(3):e002353

ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm.
Gould R, Aziz H, Woods C, Seman-Senderos M, Sparks E, Preuss C, et al
Nat. Genet. 2019 01;51(1):42-50

The mir-200 family regulates key pathogenic events in ascending aortas of individuals with bicuspid aortic valves.
Maleki S, Cottrill K, Poujade F, Bhattachariya A, Bergman O, Gådin J, et al
J. Intern. Med. 2019 Jan;285(1):102-114

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