mar
Halvtidskontroll – Anna Dieden
Projekt: "Using Targeted Proteomics to Explore Pathophysiological Pathways in CVD"
Zoom: https://lu-se.zoom.us/j/61518575013
Huvudhandledare: Martin Magnusson
Bihandledare: Amra Jujic och Petri Gudmundsson
Granskare: Magnus Dencker och Sofia Enhörning
Abstract
Background
Globally, cardiovascular diseases (CVD) are the leading cause of death, causing great personal suffering and posing a huge economic burden for society. Multiplex proteomics offer the possibility of large-scale analysis of proteins and can help identify formerly unknown pathways within the area studied. Placed in the context of CVDs, proteomics can be used as a powerful tool for finding new associations between proteins and different aspects of CVD which, in turn, may lead to improved risk-stratification, diagnosis and therapeutic targets. The aim of this thesis is to find new pathophysiological pathways associated with CVD.
Methods
The first study involved 409 black and white schoolteachers (aged 20–62) within the cohort Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA). We investigated 92 proteins within the Olink CVD III panel and their associations with different phenotypes of vascular health, namely, subclinical atherosclerosis assessed by intima media thickness, arterial stiffness assessed by pulse wave velocity, and hypertension (HT).
The second study involved 1737 subjects (aged 57–80) from the sub-cohort Malmö Preventive Project Re-examination Study (MPP-RES). Associations between the proteins were investigated regarding their associations with incident heart failure (HF) and cardiac remodeling. Significant findings were thereafter replicated in two cohorts, HOMAGE and STANISLAS. In the third study we are investigating the association between Galectin-4 (Gal-4) and diabetes in a HF cohort (HeArt and bRain failure invESTigation (HARVEST-Malmö)).
The fourth study will investigate the associations between the proteins and morbidity and mortality in HARVEST-Malmö, with significant findings to be replicated in the cohort BIOSTAT-HF.
The fifth will explore associations between the proteins and HT in MPP-RES.
Results
The results from the first project have been published in Medicine and show several new associations between proteins and the phenotypes of vascular health studied.
Preliminary results
The second study confirms previously identified proteins associated with cardiac remodeling and incident HF, while also revealing a novel protein (Gal-4) associated with incident HF. The third study has confirmed Gal-4’s role in diabetes co-existing with HF.
Significance
The associations found may, in the future, aid risk-stratification, diagnosis and the finding of new pathophysiological targets.
Publications
Dieden A, Malan L, Mels CMC, Lammertyn L, Wentzel A, Nilsson PM, Gudmundsson P, Jujic A, Magnusson M. Exploring biomarkers associated with deteriorating vascular health using a targeted proteomics chip: The SABPA study. Medicine (Baltimore). 2021;100(20):e25936.
Om evenemanget
Plats:
CRC 60-12-015, Malmö
Kontakt:
anna [dot] dieden [at] med [dot] lu [dot] se