Cardiovascular diseases

  • Article |

    MARK4 regulates cardiomyocyte contractility by promoting MAP4 phosphorylation, which facilitates the access of VASH2 to microtubules for the detyrosination of α-tubulin; MARK4 deficiency after acute myocardial infarction limits the reduction in the left ventricular ejection fraction.

    • Xian Yu
    • , Xiao Chen
    •  & Xuan Li
  • Article |

    In a cynomolgus macaque model, CRISPR base editors delivered in lipid nanoparticles are shown to efficiently and stably knock down PCSK9 in the liver to reduce levels of PCSK9 and low-density lipoprotein cholesterol in the blood.

    • Kiran Musunuru
    • , Alexandra C. Chadwick
    •  & Sekar Kathiresan
  • Article |

    Aggressive cerebral cavernous malformations (CCMs) are found to grow through a three-hit cancer-like mechanism, involving gain of function of a gene that promotes vascular growth, and loss of function of genes that suppress it.

    • Aileen A. Ren
    • , Daniel A. Snellings
    •  & Mark L. Kahn
  • Review Article |

    This Review discusses recent research that has transformed our understanding of the biology of atherosclerosis, and examines its implications for the treatment of atherosclerotic cardiovascular disease.

    • Peter Libby
  • Article |

    A genome-wide association study shows that myocardial trabeculae are an important determinant of cardiac performance in the adult heart, identifies conserved pathways that regulate structural complexity and reveals the influence of trabeculae on the susceptibility to cardiovascular disease.

    • Hannah V. Meyer
    • , Timothy J. W. Dawes
    •  & Declan P. O’Regan
  • Article
    | Open Access

    From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

    • Cristina Taddei
    • , Bin Zhou
    •  & Majid Ezzati
  • Article |

    A video-based deep learning algorithm—EchoNet-Dynamic—accurately identifies subtle changes in ejection fraction and classifies heart failure with reduced ejection fraction using information from multiple cardiac cycles.

    • David Ouyang
    • , Bryan He
    •  & James Y. Zou
  • Article |

    Cardiac stem cell therapy in mouse models of ischaemia–reperfusion injury demonstrates that improvement in heart function is linked to an immune response characterized by the induction of CCR2+ and CX3CR1+ macrophages.

    • Ronald J. Vagnozzi
    • , Marjorie Maillet
    •  & Jeffery D. Molkentin
  • Letter |

    Adoptive transfer of CAR T cells against the fibroblast marker FAP reduces cardiac fibrosis and restores function after cardiac injury in mice, providing proof-of-principle for the development of immunotherapeutic treatments for cardiac disease.

    • Haig Aghajanian
    • , Toru Kimura
    •  & Jonathan A. Epstein
  • Article |

    A disease model using cardiomyocytes derived from induced pluripotent stem cells of patients with mutated LMNA-related dilated cardiomyopathy reveals that the abnormal activation of the PDGF pathway is associated with the arrhythmic phenotypes of patients.

    • Jaecheol Lee
    • , Vittavat Termglinchan
    •  & Joseph C. Wu
  • Article |

    iNOS-driven dysregulation of the IRE1α–XBP1 pathway leads to cardiomyocyte dysfunction in mice and recapitulates the systemic and cardiovascular features of human heart failure with preserved ejection fraction.

    • Gabriele G. Schiattarella
    • , Francisco Altamirano
    •  & Joseph A. Hill
  • Letter |

    α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and human thrombomodulin require non-ischaemic preservation with continuous perfusion and post-transplantation growth control to ensure long-term orthotopic function of the xenograft in baboons.

    • Matthias Längin
    • , Tanja Mayr
    •  & Jan-Michael Abicht
  • Letter |

    Using optical mapping and 3D ultrasound, the dynamics and interactions between electrical and mechanical phase singularities were analysed by simultaneously measuring the membrane potential, intracellular calcium concentration and mechanical contractions of the heart during normal rhythm and fibrillation.

    • J. Christoph
    • , M. Chebbok
    •  & S. Luther
  • Article |

    High salt intake changed the gut microbiome and increased TH17 cell numbers in mice, and reduced intestinal survival of Lactobacillus species, increased the number of TH17 cells and increased blood pressure in humans.

    • Nicola Wilck
    • , Mariana G. Matus
    •  & Dominik N. Müller
  • Letter |

    Fibroblast-specific Il-11 expression causes heart and kidney fibrosis and organ failure, whereas IL-11 inhibition prevents fibroblast activation and organ fibrosis, indicating that IL-11 inhibition is a potential therapeutic strategy to treat fibrotic diseases.

    • Sebastian Schafer
    • , Sivakumar Viswanathan
    •  & Stuart A. Cook
  • Letter |

    Deletion of the Hippo pathway component Salvador in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function.

    • John P. Leach
    • , Todd Heallen
    •  & James F. Martin
  • Article |

    The extracellular matrix protein agrin promotes cardiac regeneration in adult mice after myocardial infarction; it modulates cardiac differentiation and proliferation by interacting with the dystrophin–glycoprotein complex, Yap and ERK-mediated signalling.

    • Elad Bassat
    • , Yara Eid Mutlak
    •  & Eldad Tzahor
  • Article |

    Lipopolysaccharide derived from gut bacteria can accelerate the formation of cerebral cavernous malformations by activating TLR4 on endothelial cells, and polymorphisms that increase expression of the genes encoding TLR4 or its co-receptor CD14 are associated with higher CCM lesion burden in humans.

    • Alan T. Tang
    • , Jaesung P. Choi
    •  & Mark L. Kahn
  • Letter |

    Multi-ancestry genome-wide association analyses for birth weight in 153,781 individuals identified 60 genomic loci in which birth weight and fetal genotype were associated and found an inverse genetic correlation between birth weight and cardiometabolic risk.

    • Momoko Horikoshi
    • , Robin N. Beaumont
    •  & Rachel M. Freathy
  • Letter |

    Atherosclerotic lesions in mice and humans switch on a ‘don’t eat me’ signal—expression of CD47—that prevents effective removal of diseased tissue; anti-CD47 antibody therapy can normalize this defective efferocytosis, with beneficial results in several mouse models of atherosclerosis.

    • Yoko Kojima
    • , Jens-Peter Volkmer
    •  & Nicholas J. Leeper
  • Article |

    Myocardial hypoxia activates HIF1α, which activates the splicing factor SF3B1, which mediates a splice switch of the fructose-metabolising enzyme KHK, so that the C isoform that has superior affinity for fructose is expressed in the heart—pathological heart growth and contractile dysfunction can therefore be suppressed by depleting SF3B1 or deleting KHK.

    • Peter Mirtschink
    • , Jaya Krishnan
    •  & Wilhelm Krek
  • Article |

    This study shows that cardiac injury induces cardiac fibroblasts to undergo mesenchymal–endothelial transition and acquire an endothelial-cell like fate, a process mediated, in part, by a p53-dependent mechanism — use of a small molecule activator of p53 increases mesenchymal–endothelial transition, leading to reduced scarring and better preservation of heart function.

    • Eric Ubil
    • , Jinzhu Duan
    •  & Arjun Deb
  • Letter |

    Here, a long noncoding RNA, termed Mhrt, is identified in the loci of myosin heavy chain (Myh) genes in mice and shown to be capable of suppressing cardiomyopathy in the animals, as well as being repressed in diseased human hearts.

    • Pei Han
    • , Wei Li
    •  & Ching-Pin Chang
  • Letter |

    During development of myointimal hyperplasia in human arteries, smooth muscle cells have hyperpolarized mitochondrial membrane potential (ΔΨm), high proliferation and apoptosis resistance; PDK2 is a key regulatory protein whose activation is necessary for myointima formation, and its blockade with dichloroacetate prevents Δψm hyperpolarization, facilitates apoptosis and reduces myointima formation in injured arteries, without preventing vessel re-endothelialization, possibly representing a novel strategy to prevent proliferative vascular diseases.

    • Tobias Deuse
    • , Xiaoqin Hua
    •  & Sonja Schrepfer
  • Letter |

    Reduced activity of the calcium-transporting ATPase SERCA2a is a hallmark of heart failure; here, microRNAs that downregulate SERCA2a function are identified, and antagonism of one, miR-25, is shown to halt heart failure in mice.

    • Christine Wahlquist
    • , Dongtak Jeong
    •  & Mark Mercola
  • Letter |

    A role is demonstrated for miR-34a, a microRNA that is upregulated in the ageing heart; miR-34a downregulates PNUTS, a protein that protects cardiomyocytes and telomeres, silencing of miR-34a is therefore a promising therapeutic target.

    • Reinier A. Boon
    • , Kazuma Iekushi
    •  & Stefanie Dimmeler
  • Article |

    The human heart regenerates poorly, causing insufficient healing after injury; here, microRNAs screened for the ability to induce cardiomyocyte proliferation are shown to stimulate cardiac regeneration and almost complete recovery of the heart after infarction.

    • Ana Eulalio
    • , Miguel Mano
    •  & Mauro Giacca