Research articles

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  • Despite an emerging role for cerebrovascular endothelial cells in a range of neurological pathologies, AAV vector development to date has focused on tools designed to target neurons or astrocytes. Here, Krolak et al. describe a specific variant of AAV (AAV-BI30), with high specificity and efficacy for transduction of endothelial cells across the central nervous system.

    • Trevor Krolak
    • Ken Y. Chan
    • Benjamin E. Deverman
    Technical Report
  • Huang et al. show that myocardial infarction (MI)-associated vasculature is structurally and functionally abnormal, impeding vessel function and cardiac repair in mice. Analyses of the transcriptome of the cardiac endothelium after MI identify a PDGF–NF-κB–HIF-1α Snail axis responsible for mesenchymal transformation of endothelial cells and show that genetic ablation or targeted disruption of PDGF signaling normalizes vasculature and improves cardiac function recovery after MI.

    • Menggui Huang
    • Fan Yang
    • Yanqing Gong
  • Cheng et al. show that smooth muscle cell (SMC)-specific deletion of Smad3 influences the fate of de-differentiated SMCs in atherosclerotic plaques in vivo, promoting both a pro-remodeling SMC transition phenotype and expansion of the SMC-derived chondromyocyte population. These cellular changes are associated with increased outward remodeling and plaque calcification.

    • Paul Cheng
    • Robert C. Wirka
    • Thomas Quertermous
  • O’Regan and colleagues use deep-learning cardiac motion analysis in participants of the UK Biobank to measure diastolic functional traits and perform a genome-wide association study to generate insights into the genetic and environmental factors that influence diastolic function.

    • Marjola Thanaj
    • Johanna Mielke
    • Declan P. O’Regan
    ArticleOpen Access
  • Popescu et al. developed a deep learning approach that blends neural networks and survival analysis to predict patient-specific survival curves from raw contrast-enhanced cardiac magnetic resonance images and clinical covariates for patients with ischemic heart disease to offer accurate arrhythmic sudden death predictions.

    • Dan M. Popescu
    • Julie K. Shade
    • Natalia A. Trayanova
    ArticleOpen Access
  • Zong and colleagues reveal a critical role for the ion channel TRPM2 in macrophages through mediating reactive oxygen species production, inflammasome activation, oxidized LDL uptake and subsequently inflammatory responses, which they show is mediated by CD36 activity, thereby establishing a mutually regulating and positive feedback mechanism between CD36 and TRPM2 in atherogenesis.

    • Pengyu Zong
    • Jianlin Feng
    • Lixia Yue
  • Koenig et al. present integrated single-cell and single-nucleus RNA-sequencing data of cardiac samples obtained from 27 healthy donors and 18 individuals with dilated cardiomyopathy. This extensive resource provides insights on cell composition and gene expression changes driven by the disease status, sex or age of the patients.

    • Andrew L. Koenig
    • Irina Shchukina
    • Kory J. Lavine
    ResourceOpen Access
  • Snellings et al. show that an identical PIK3CA mutation is found in both developmental venous anomalies (DVAs) and associated cerebral cavernous malformations (CCMs). However, an activating MAP3K3 mutation appears only in CCMs, supporting a mechanism where DVAs develop as the result of a PIK3CA mutation.

    • Daniel A. Snellings
    • Romuald Girard
    • Douglas A. Marchuk
  • Jarr and colleagues show that statins augment efferocytosis by inhibiting the nuclear translocation of NF-κB1 p50 and suppressing the expression of the key ‘don’t-eat-me’ molecule CD47, which in part explains the pleiotropic effects of statins and provides a basis for future translational efforts.

    • Kai-Uwe Jarr
    • Jianqin Ye
    • Nicholas J. Leeper
  • In a multicenter research program coordinated by the International Mouse Phenotyping Consortium, Spielmann et al. analyze the cardiac function and structure in ~4,000 monogenic mutant mice and identify 705 mouse genes involved in cardiac function, 75% of which have not been previously linked to cardiac heritable disease in humans. Using the UK Biobank human data, the authors validate the link between cardiovascular disease and some of the newly identified genes to illustrate the resource value and potential of their mutant mouse collection.

    • Nadine Spielmann
    • Gregor Miller
    • Martin Hrabe de Angelis
    ArticleOpen Access
  • Song and colleagues show that FDA-approved cough suppressant dextromethorphan could be used as an agonist of sigma non-opioid intracellular receptor 1 (SIGMAR1) to normalize the action potential in human cellular models and a mouse model of Timothy syndrome, a congenital disease with no available treatment. The researchers also show that dextromethorphan normalizes the action potential in human cellular models of two additional inherited cardiac arrhythmias: long QT syndrome types 1 and 2, which are caused by mutations in different genes.

    • LouJin Song
    • Ramsey Bekdash
    • Masayuki Yazawa
  • Using large-scale single-nucleus transcriptomics, Nicin et al. report insights into human cardiac hypertrophy, caused by pressure overload, at single-cell resolution. The authors show that intercellular communication, particularly via the Eph receptor tyrosine kinase EPHB1, is impaired in human cardiomyopathy.

    • Luka Nicin
    • Sam Michael Schroeter
    • Stefanie Dimmeler
    ResourceOpen Access
  • Honigberg and colleagues analyzed the frequency of depressed mood in conjunction with polygenic risk scores for coronary artery disease (CAD), type 2 diabetes (T2D) and atrial fibrillation in the UK Biobank and showed that depressed mood was independently associated with a lower risk of CAD and T2D across the cardiometabolic polygenic risk spectrum.

    • Michael C. Honigberg
    • Yixuan Ye
    • Pradeep Natarajan
  • Koplev et al. apply interactive system analyses to infer and characterize gene-regulatory networks (GRNs) active within and across tissues that cause cardiometabolic disease and coronary artery disease (CAD). By including GWAS in the integrative analysis, the provided multiorgan framework of GRNs is suggested to explain significantly more heritability of CAD than what has been achieved by analyzing GWAS alone.

    • Simon Koplev
    • Marcus Seldin
    • Johan L. M. Björkegren