Publications by authors named "Markus Ramste"

Article Synopsis
  • The study connects genetic variants linked to coronary artery disease (CAD) with cellular and molecular traits by analyzing chromatin accessibility and gene expression in human coronary arteries.
  • Through single-cell analysis, researchers identified thousands of specific chromatin accessibility loci (caQTLs) and found that smooth muscle cells (SMCs) are particularly susceptible to genetic risks associated with CAD.
  • They developed a comprehensive mapping approach to trace disease variants to potential causal genes across different cell types and confirmed their findings using advanced techniques like genome-wide Hi-C and CRISPR interference.
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Objective: Although the incidence and case fatality (CF) of acute myocardial ischaemic syndrome (AMIS) have declined in recent decades, some studies have suggested a potential stagnation in this decline. We examined if a similar development in AMIS trends can be observed in Finland from 1996 to 2021 among persons aged 35-74 years.

Methods: We linked Finnish country-wide Hospital Discharge- and Causes of Death- Registers covering the first non-fatal and fatal myocardial ischaemic events (total 69 906 442 person-years at risk).

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Introduction: Environmental exposure to dioxin has been linked to increased myocardial infarction. Smooth muscle cells (SMC) in the coronary vasculature play a critical role in atherosclerotic plaque remodeling due to their phenotypic plasticity, however, the detailed mechanism linking dioxin exposure to adverse SMC modulation is not well understood.

Methods: Single-cell RNA and ATAC sequencing and histological analyses were performed on the aorta from mouse models of atherosclerosis exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) or control.

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Article Synopsis
  • * A meta-analysis identified eight genetic loci linked to Raynaud's syndrome, with specific genes like ADRA2A, NOS3, and IRX1 showing important roles in blood vessel behavior and gene expression.
  • * The research utilized CRISPR gene editing and functional assays, revealing how these genes influence blood vessel contraction in response to cold, emphasizing the complexity of genes in understanding this syndrome.
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Unlabelled: Mapping the genomic architecture of complex disease has been predicated on the understanding that genetic variants influence disease risk through modifying gene expression. However, recent discoveries have revealed that a significant burden of disease heritability in common autoinflammatory disorders and coronary artery disease is mediated through genetic variation modifying post-transcriptional modification of RNA through adenosine-to-inosine (A-to-I) RNA editing. This common RNA modification is catalyzed by ADAR enzymes, where ADAR1 edits specific immunogenic double stranded RNA (dsRNA) to prevent activation of the double strand RNA (dsRNA) sensor MDA5 ( ) and stimulation of an interferon stimulated gene (ISG) response.

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Background: Preclinical studies have shown the therapeutic potential of VEGF-B (vascular endothelial growth factor B) in revascularization of the ischemic myocardium, but the associated cardiac hypertrophy and adverse side effects remain a concern. To understand the importance of endothelial proliferation and migration for the beneficial versus adverse effects of VEGF-B in the heart, we explored the cardiac effects of autocrine versus paracrine VEGF-B expression in transgenic and gene-transduced mice.

Methods: We used single-cell RNA sequencing to compare cardiac endothelial gene expression in VEGF-B transgenic mouse models.

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Article Synopsis
  • - This review discusses how genome-wide association studies (GWAS) are used to find the underlying causes of vascular disease risk by identifying specific genes and their functions.
  • - It explains the history and methods of GWAS, including the use of data imputation and collaborative meta-analyses to enhance research power and consistency in findings.
  • - The conclusions highlight that GWAS is transforming cardiovascular disease research, leading to better understanding of genetic factors and potential pathways for developing targeted therapies.
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Our aim was to investigate in a real-life prospective patient cohort how CYP2C19 loss-of-function (LOF) variants and CYP2C19 inhibitor omeprazole or esomeprazole influence the incidence of cardiovascular events in patients using clopidogrel. Data based simultaneously on these factors are conflicting and sparse. A cohort of prospective patients (n = 1972) with acute coronary syndrome (n = 1302) or symptomatic chronic coronary disease (n = 656) was followed for 365 days after hospitalization with information on purchased prescription drugs, hospital discharge, death, and genotype for CYP2C19*2, CYP2C19*3, and CYP2C19*8 LOF variants.

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