Biochemistry articles within Nature Reviews Cardiology

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  • Comment |

    Low plasma levels of HDL cholesterol are a risk factor for infection and hospitalization for infectious disease. Recent work suggests that inadequate levels of HDL particles of specific sizes — small and medium — account for this risk. In this Comment, we discuss the mechanistic implications of these observations and the methodologies used to quantify HDL size.

    • Jay W. Heinecke
    •  & W. Sean Davidson

  • Research Highlight |

    A new study has identified a scavenger receptor-independent mechanism of atherosclerosis development by showing that LDL uptake through macropinocytosis contributes to macrophage foam cell formation and atherosclerosis development and that an FDA-approved drug that inhibits macropinocytosis inhibits atherosclerosis development in mice.

    • Irene Fernández-Ruiz

  • Review Article |

    In this Review, McGarrah and White outline the major factors regulating branched-chain amino acid (BCAA) abundance and metabolic fate, highlight molecular mechanisms connecting impaired BCAA homeostasis to cardiovascular disease and discuss the epidemiological evidence connecting BCAAs with various cardiovascular disease states.

    • Robert W. McGarrah
    •  & Phillip J. White

  • Review Article |

    Peripartum cardiomyopathy (PPCM) is a rare form of heart failure that presents in late pregnancy or early in the postpartum period. In this Review, Hoes and colleagues discuss the known risk factors for PPCM, including genetic variants and pre-eclampsia, and describe the potential pathogenic mechanisms underlying the development of PPCM such as disrupted metabolic homeostasis in the heart owing to pregnancy-induced hormone fluctuations.

    • Martijn F. Hoes
    • , Zoltan Arany
    •  & Peter van der Meer

  • Review Article |

    Fatty acids affect the pathogenesis of atherosclerosis, and accumulating evidence shows that fatty acids also modulate T cell functions and processes. This Review summarizes the effects of circulating fatty acids on the metabolism, activation, proliferation and polarization of T cells and how these changes influence the subsequent functions of T cells in the pathogenesis of atherosclerosis.

    • Nathalie A. Reilly
    • , Esther Lutgens
    •  & J. Wouter Jukema

  • Review Article |

    In this Review, Gotto and colleagues summarize the evolution of our understanding of HDL structure and function, current models of atheroprotection by HDL involving reverse cholesterol transport, and their identification of a correlation between the bioavailability of free cholesterol contained in HDL and atherogenesis.

    • Henry J. Pownall
    • , Corina Rosales
    •  & Antonio M. Gotto Jr

  • Research Highlight |

    Deficiency in the orphan G protein-coupled receptor 146 (GPR146) decreases blood lipid levels and protects against atherosclerosis in mice independently of LDL receptor activity, according to a new study.

    • Irene Fernández-Ruiz

  • Review Article |

    This Review summarizes the role of transcription factors and epigenetic remodelling in modulating macrophage plasticity, provides an overview of the cooperative action of transcription factors and epigenetic modifiers controlling macrophage activation in the context of atherosclerosis and inflammation, and highlights the therapeutic potential of modulating transcription factor activity.

    • Tatyana Kuznetsova
    • , Koen H. M. Prange
    •  & Menno P. J. de Winther

  • Research Highlight |

    Two studies reporting novel insights into fibroblast identity and activation dynamics provide an important step forward in our understanding of cardiac fibrosis and the quest to develop new anti-fibrotic strategies

    • Irene Fernández-Ruiz

  • Review Article |

    Conflicting findings about the effects of testosterone replacement therapy on the risk of cardiovascular disease have been reported in various studies and clinical trials. In this Review, Gagliano-Jucá and Basaria discuss the design, outcomes and shortcomings of studies on testosterone replacement therapy, as well as studies examining the cardiovascular effects of testosterone in vitro, in animals and in humans.

    • Thiago Gagliano-Jucá
    •  & Shehzad Basaria

  • Review Article |

    Dietary fats comprise heterogeneous molecules with diverse structures and complex health effects. This Review discusses the effects of different dietary fats on cell processes and cardiometabolic disease risk factors and clinical events, highlighting areas of controversy and future research directions to improve the prevention and management of cardiometabolic diseases through optimization of dietary fat intake.

    • Jason H. Y. Wu
    • , Renata Micha
    •  & Dariush Mozaffarian

  • Research Highlight |

    New research on the direct effects of stress on the heart highlights the importance of the balance of stress hormone signalling through glucocorticoid receptors and mineralocorticoid receptors in cardiomyocytes to maintain cardiac health.

    • Irene Fernández-Ruiz

  • Research Highlight |

    The scavenger receptor class B member 1 (SRB1) in endothelial cells mediates active transcellular transport of circulating LDL into the artery wall and thereby drives the accumulation of LDL in macrophages, which become foam cells and promote the development of atherosclerosis

    • Irene Fernández-Ruiz

  • Research Highlight |

    Singlet molecular oxygen generated by endothelial indoleamine 2,3-dioxygenase 1 has an important pathophysiological role in mammals in the redox regulation of arterial relaxation and blood pressure during inflammatory conditions through the formation of a tryptophan-derived metabolite

    • Irene Fernández-Ruiz

  • Comment |

    LDL cholesterol is an important contributor to the risk of coronary heart disease, and its measurement is central to evaluating the effects of lipid-modifying therapies. Several ‘LDL-cholesterol’ assays exist but their methodologies differ, leading to between-assay heterogeneity in values of ‘LDL cholesterol’. We advocate the need for awareness of the potential implications.

    • Michael V. Holmes
    •  & Mika Ala-Korpela

  • Review Article |

    In this Review, Boffa and Koschinsky discuss the role of lipoprotein(a) (Lp(a)) as a risk factor for atherothrombotic cardiovascular disease and calcific aortic valve disease, highlighting the important function of oxidized phospholipid modifications of Lp(a), which elicit harmful signalling processes in the arterial wall and the valve leaflet, in mediating the effects of this lipoprotein on both disorders.

    • Michael B. Boffa
    •  & Marlys L. Koschinsky

  • Review Article |

    Transient receptor potential (TRP) channels are a family of 28 nonselective cationic channels that are heterogeneously expressed in different regions and cell types of the heart. In this Review, the authors summarize the various physiological and pathological cardiac processes in which TRP channels are involved.

    • Thomas Hof
    • , Sébastien Chaigne
    •  & Romain Guinamard

  • Research Highlight |

    The polyploidy of mammalian cardiomyocytes is a barrier to heart regeneration, but modification of the cardiomyocyte cell cycle can boost their regenerative potential.

    • Paulina Strzyz

  • Review Article |

    The identification of mutations in ion channels has been crucial to understanding the pathogenesis of cardiac arrhythmias, but the aetiology of a considerable number of arrhythmogenic disorders remains unknown. In this Review, Lazzerini and colleagues discuss the role of autoimmunity in the pathogenesis of cardiac arrhythmias, describing how different autoantibodies against ion channels in the heart participate in the development of these conditions.

    • Pietro Enea Lazzerini
    • , Pier Leopoldo Capecchi
    •  & Mohamed Boutjdir

  • Review Article |

    Thyroid hormones have an important role in maintaining cardiovascular homeostasis, and subtle changes in thyroid hormone concentrations adversely influence the cardiovascular system. In this Review, Jabbar et al. discuss the role of thyroid hormones in the pathogenesis and management of cardiovascular diseases such as heart failure and acute myocardial infarction, and outline the utility of therapy with thyroid hormones for the management of these conditions.

    • Avais Jabbar
    • , Alessandro Pingitore
    •  & Salman Razvi

  • Review Article |

    Ca2+ cycling defects in cardiac myocytes are a hallmark of heart failure. Roger Hajjar and colleagues discuss the association between abnormalities in sarcoplasmic reticulum Ca2+handling proteins and heart failure as well as the potential therapeutic benefits of novel treatment strategies that target these proteins.

    • Changwon Kho
    • , Ahyoung Lee
    •  & Roger J. Hajjar

  • Review Article |

    Metabolomics is emerging as a powerful tool for the investigation of the molecular mechanisms of cardiovascular disease, including atherosclerosis, ischemia, myocardial infarction, and heart failure. In this Review, the authors discuss advances in the use of NMR spectroscopy and mass spectrometry, particularly in field of lipidomics, and in the search for novel biomarkers of cardiac disease.

    • Julian L. Griffin
    • , Helen Atherton
    •  & Luigi Atzori

  • News & Views |

    New therapeutic strategies are needed for patients with atherosclerosis. Despite failing to reach its primary end point, a multicenter, phase II, randomized, placebo-controlled trial of RVX-208—an oral, synthetic quinazoline molecule that stimulates expression of endogenous apolipoprotein A-I—has provided somewhat encouraging results. Nevertheless, detailed investigations are still needed if we are ever to realize the full atheroprotective potential of novel HDL-targeted therapies.

    • Prediman K. Shah

  • Review Article |

    The relationship between an elevated level of LDL cholesterol (LDL-C) and increased risk of cardiovascular disease is well established. National and international guidelines are continuously being revised to recommend increasingly lower LDL-C targets for cardiovascular disease prevention. In this Review, Drs. Brautbar and Ballantyne examine the evidence and recommendations for optimal LDL-C levels and the agents currently available or under development to achieve these levels.

    • Ariel Brautbar
    •  & Christie M. Ballantyne

  • Review Article |

    Although high levels of HDL seem to be protective against clinical events from atherosclerosis, assessing the composition and function of HDL is a more-accurate approach to determine cardiovascular risk. The authors of this Review describe the atheroprotective effects of HDL, which have been attributed to its anti-inflammatory properties and role in cholesterol efflux. The relationship between impaired HDL function and cardiovascular disease is also discussed, as well as approaches to evaluate HDL functionality.

    • Mohamad Navab
    • , Srinivasa T. Reddy
    •  & Alan M. Fogelman

  • Review Article |

    The benefits of lowering LDL-cholesterol levels to prevent clinical events are well-recognized. However, other parameters of the lipoprotein–lipid profile are likely to contribute to cardiovascular risk and should be used in addition to the traditional lipid profile for improved assessment of cardiovascular risk. The authors of this Review discuss alternative and emerging lipid parameters associated with cardiovascular disease that could identify patients at high risk and those who will benefit most from lipid-lowering therapy.

    • Benoit J. Arsenault
    • , S. Matthijs Boekholdt
    •  & John J. P. Kastelein

  • News & Views |

    The 'funny' current (If) has been the subject of 30 years of laboratory research and is an important therapeutic target in heart disease owing to its effects on heart rate. SHIFT, a trial in patients with all-cause heart failure, shows that If inhibition reduces combined mortality and rate of hospitalization and opens further avenues of research and therapeutic challenges.

    • Cesare M. Terracciano
    •  & Magdi H. Yacoub

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