Visual Universitätsmedizin Mainz

TRP X31 - Comparative analysis of platelet transcriptome signatures in obesity

Funding period: 01.01.2019 - 31.08.2020

Project Summary

State of the art

Obesity is one of the major health problems in the world; the WHO estimates that in 2016 39% of men and women aged 18+ were overweight (body mass index; 25 ≤ BMI < 30 kg/m2) and 11% of men and 15% of women were obese (BMI ≥ 30 kg/m2). Excessive and i.e. abnormal ectopic (i.e. visceral) fat accumulation presents one of the major risk factors for thrombotic disorders, such as cardiovascular disease, stroke, and venous thromboembolism due to the associated cluster of pathogenic factors comprising adipose tissue-derived low-grade chronic inflammation (e.g. CRP, IL-6, TNF-α), insulin resistance and oxidative stress (e.g. lipid peroxidation). Platelet hyper-reactivity plays a central role in accelerating thrombotic events in obesity (BMI over 30 kg/m2). For example, loss of platelet inhibition by insulin has been suggested as a major determinant of platelet hyperactivity in obese patients. It is known that insulin inhibits splicing of tissue factor (TF) pre-mRNA in platelets; diabetic complications of obesity may therefore contribute independently to the thrombogenicity of the platelets and atherothrombosis. Furthermore, obese adolescents have significantly increased Mean Platelet Volume (MPV) as compared to their healthy peers, indicating broader changes in platelet phenotypes.

Hypothesis

We hypothesize that diabetic complications of obesity produce distinct change in platelet transcriptomes that can be used as risk indicator for cardiovascular events. We propose to bridge basic mechanistic and epidemiological approaches to define platelet transcriptome changes distinguishing obese individuals with metabolic complications from obese as well as normal weight individuals.

Principal Investigators

Ruf, MD
Professor Wolfram Ruf, MD
Position: Scientific Director CTH, Alexander von Humboldt-Professorship "Experimental Hemostasiology", Deputy Speaker of CTH, Deputy Speaker of CTVB, Principal Investigator DZHK

06131 17-8222
06131 17-3456
ruf@uni-mainz.de

Wild, MD, MSc
Professor Philipp Wild, MD, MSc
Position: Preventive Cardiology and Medical Prevention, Professorship „Clinical Epidemiology“, Coordinator Gutenberg Health Study (GHS), Principal Investigator Deutsches Zentrum für Herz-Kreislaufforschung (DZHK)