Biology subjects

Steinhagen-Thiessen, E.

Publications and source records attributed to Steinhagen-Thiessen, E..

4 recordsLinked to original sources

bioRxiv2019

Cohort profile: The LipidCardio Study - Role of Lipoproteins in Cardiovascular Disease

PurposeThe LipidCardio Study was established for in-depth analyses of cardiovascular risk factors, providing well-defined cardiovascular and metabolic phenotypes. Particularly the role of lipoproteins in the pathobiological process and treatment of cardiovascular disease will be a main focus.\n\nParticipants1.005 individuals aged 21 years and older undergoing cardiac catheterization during 17 months at a tertiary academic cardiology center were enrolled. The baseline data set contains detailed phenotyping, broad biochemical parameters, genetic data, but also standardized personal and family history, a screening test for cognitive impairment, pulse wave analysis and measurements of hand grip strength, amongst others. Blood samples were stored in a biobank for future analyses.\n\nFindings to dateThe mean age of the participants at enrolment was 70.9{+/-}11.1 years (70% male). Coronary angiography provided evidence of obstructive coronary artery disease (CAD) in 69.9% of participants. Those with evidence of CAD were significantly more likely to be male, inactive, diabetic and with a family history of cardiovascular disease than participants without CAD.\n\n20% of patients had lipoprotein(a) [Lp(a)] concentrations above 106.9 nmol/L (fifth quintile). These patients had significantly increased odds of obstructive CAD compared to participants in quintiles 1-4 (OR 1.70, 95% CI 1.17 to 2.48, p=0.005). There was reasonable evidence that with increasing severity of CAD the odds of having elevated Lp(a) increased. We were able to replicate the established strong association between specified single nucleotide polymorphisms (SNPs) in the LPA gene (rs10455872, rs3798220 and rs186696265) and the APOE gene (rs7412), and the concentration of Lp(a), validating our phenotype database and biobank.\n\nFuture plansMortality information will be obtained in two-year intervals. Follow-up phone interviews will be conducted at 3, and 6 years after enrolment. We seek to cooperate with other researchers in the field, e.g. by sharing data and biobank samples.\n\nRegistrationnot applicable, purely observational study

epidemiology↗

bioRxiv2019

Cis-epistasis at the LPA locus and risk of coronary artery disease

Identification of epistasis affecting complex human traits has been challenging. Focusing on known coronary artery disease (CAD) risk loci, we explore pairwise statistical interactions between 8,068 SNPs from ten CAD genome-wide association studies (n=30,180). We discovered rs1800769 and rs9458001 in the vicinity of the LPA locus to interact in modulating CAD risk (P=1.75x10-13). Specific genotypes (e.g., rs1800769 CT) displayed either significantly decreased or increased risk for CAD in the context of genotypes of the respective other SNP (e.g., rs9458001 GG vs. AA). In the UK Biobank (n=450,112) significant interaction of this SNP pair was replicated for CAD (P=3.09x10-22), and was also found for aortic valve stenosis (P=6.95x10-7) and peripheral arterial disease (P=2.32x10-4). Identical interaction patterns affected circulating lipoprotein(a) (n=5,953; P=8.7x10-32) and hepatic apolipoprotein(a) (apo(a)) expression (n=522, P=2.6x10-11). We further interrogated potential biological implications of the variants and propose a mechanism explaining epistasis that ultimately may translate to substantial cardiovascular risks.

genetics↗

bioRxiv2018

Influence of nutritional tyrosine on cognition and functional connectivity in healthy old humans

Tyrosine is precursor for monoamine neurotransmitters such as dopamine (DA), which is one of the key neurotransmitters in the frontostriatal network and of crucial relevance for mental disorders. Recent research reported that high dose tyrosine application resulted in increased brain DA synthesis, which is consistent with the observation of positive associations between daily tyrosine intake and cognitive test performance. In the present study, we investigated the associations between working memory (WM) dependent tasks and self-reported nutritional tyrosine intake within a large group of healthy elderly humans (286 subjects) by additionally including brain functional data. We observed a negative correlation between tyrosine intake and resting-state functional connectivity (rsFC) between the striatum (putamen) and the prefrontal cortex. That is to say, we found higher rsFC in individuals consuming less tyrosine per day. At the same time, this increased rsFC or hyperconnectivity was associated with lower WM performance. These findings suggest that lower or insufficient supply of tyrosine might result in dysfunctional connectivity between striatal and frontal regions leading to lower WM capacity in healthy elderly humans.

neuroscience↗

bioRxiv2018

An eicosanoid protects from statin-induced myopathic changes in primary human cells

Statin-related muscle side effects are a constant healthcare problem since patient compliance is dependent on side effects. Statins reduce plasma cholesterol levels and can prevent secondary cardiovascular disease. Although statin-induced muscle damage has been studied, preventive or curative therapies are yet to be reported.\n\nWe exposed primary human muscle cell populations (n=25) to a lipophilic (simvastatin) and a hydrophilic (rosuvastatin) statin and analyzed their expressome. Data and pathway analyses included GOrilla, Reactome and DAVID. We measured mevalonate intracellularly and analyzed eicosanoid profiles secreted by human muscle cells. Functional assays included proliferation and differentiation quantification.\n\nMore than 1800 transcripts and 900 proteins were differentially expressed after exposure to statins. Simvastatin had a stronger effect on the expressome than rosuvastatin, but both statins influenced cholesterol biosynthesis, fatty acid metabolism, eicosanoid synthesis, proliferation, and differentiation of human muscle cells. Cultured human muscle cells secreted {omega}-3 and {omega}-6 derived eicosanoids and prostaglandins. The {omega}-6 derived metabolites were found at higher levels secreted from simvastatin-treated primary human muscle cells. Eicosanoids rescued muscle cell differentiation.\n\nOur data suggest a new aspect on the role of skeletal muscle in cholesterol metabolism. For clinical practice, the addition of omega-n fatty acids could be suitable to prevent or treat statin-myopathy.

molecular biology↗