Featured
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Article |
Neuroimmune cardiovascular interfaces control atherosclerosis
The peripheral nervous system uses neuroimmune cardiovascular interfaces to assemble a structural artery–brain circuit, and therapeutic intervention in the artery–brain circuit attenuates atherosclerosis.
- Sarajo K. Mohanta
- , Li Peng
- & Andreas J. R. Habenicht
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Article |
PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism
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
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Review Article |
The changing landscape of atherosclerosis
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
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Article |
ALDH4A1 is an atherosclerosis auto-antigen targeted by protective antibodies
An autoantibody found in a mouse model of atherosclerosis recognizses ALDH4A1, and infusion of the antibody delays plaque formation in mice.
- Cristina Lorenzo
- , Pilar Delgado
- & Almudena R. Ramiro
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Letter |
Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death
Histone H4 is released from neutrophil extracellular traps and induces membrane lysis in vascular smooth muscle cells, leading to the destabilization of atherosclerotic plaques.
- Carlos Silvestre-Roig
- , Quinte Braster
- & Oliver Soehnlein
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Letter |
SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis
The SR-B1 receptor partners with DOCK4 and RAC1 to drive the uptake and transcytosis of LDL in endothelial cells, thereby promoting atherosclerosis in mice.
- Linzhang Huang
- , Ken L. Chambliss
- & Philip W. Shaul
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Letter |
Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice
A single-chain variable fragment of the antibody E06, which binds to the phosphocholine headgroup of oxidized phospholipids, blocks the uptake of oxidized low-density lipoprotein by macrophages, and reduces inflammation and atherosclerosis in hypercholesterolaemic mice.
- Xuchu Que
- , Ming-Yow Hung
- & Joseph L. Witztum
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Article |
Endothelial TLR4 and the microbiome drive cerebral cavernous malformations
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
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Letter |
Integrin-YAP/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow
YAP and TAZ, effectors of the Hippo pathway, sense mechanical forces generated by blood flow and play a role in atherosclerosis pathogenesis.
- Li Wang
- , Jiang-Yun Luo
- & Yu Huang
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Letter |
Control of mitochondrial function and cell growth by the atypical cadherin Fat1
Fragments of the atypical cadherin Fat1 accumulate in the mitochondria of vascular smooth muscle cells where they reduce respiration, leading to a regulated proliferative response to arterial injury.
- Longyue L. Cao
- , Dario F. Riascos-Bernal
- & Nicholas E. S. Sibinga
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Letter |
CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis
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
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Letter |
Cerebral cavernous malformations arise from endothelial gain of MEKK3–KLF2/4 signalling
Gain of MEKK3 signalling is shown to cause cerebral cavernous malformations (CCMs) via activation of the target genes Klf2 and Klf4; endothelial-specific loss of MEKK3, KLF2 or KLF4 prevents lesion formation and lethality in a mouse CCM model.
- Zinan Zhou
- , Alan T. Tang
- & Mark L. Kahn
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Letter |
The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia
Zinc transporter ZIP12 expression is increased in many cell types in remodelled mammalian pulmonary arterioles in hypoxia-induced pulmonary hypertension.
- Lan Zhao
- , Eduardo Oliver
- & Martin R. Wilkins
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Outlook |
Cardiovascular disease: Biochemistry to behaviour
Cardiovascular disease (CVD) remains the grim reaper's primary calling card, but people can take steps to keep the world's number one killer at bay.
- Bill Cannon
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Outlook |
Pathology: At the heart of the problem
Research is illuminating the molecular mechanisms that can cascade into debilitating heart disease.
- Cassandra Willyard
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Outlook |
Physiology: Beating stroke
New drugs and more focused therapy might cut down on atrial fibrillation and reduce the incidence of stroke.
- Neil Savage
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Research Highlights |
Fatty plaque link to inflammation
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News |
Animals engineered with pinpoint accuracy
More accurate genetic modification has created allergen-free cow's milk and pigs that could serve as a model for atherosclerosis.
- Amy Maxmen
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Research Highlights |
Nanoparticles home in to clear clots
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Research Highlights |
Stem cells from blood vessels
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Letter |
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A
The APOE4-mediated proinflammatory pathway is shown to initiate blood–brain barrier breakdown and resulting neurodegeneration in transgenic mice.
- Robert D. Bell
- , Ethan A. Winkler
- & Berislav V. Zlokovic
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Research Highlights |
Culprits in diabetic heart risk
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Research Highlights |
Stranded cells fuel plaques
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Review Article |
Progress and challenges in translating the biology of atherosclerosis
- Peter Libby
- , Paul M Ridker
- & Göran K. Hansson
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Letter |
Recapitulation of premature ageing with iPSCs from Hutchinson–Gilford progeria syndrome
- Guang-Hui Liu
- , Basam Z. Barkho
- & Juan Carlos Izpisua Belmonte
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Letter |
9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response
A non-coding region on chromosome 9p21 was previously shown to associate with coronary artery disease and type 2 diabetes, and the region has been implicated in regulating neighbouring genes. Here, 33 distinct enhancers within this region are identified, showing that SNPs in one of the enhancers affect STAT1 binding. Furthermore, it is shown that in human vascular endothelial cells the enhancer interval physically interacts with a number of specific loci and that IFN-γ activation strongly affects the chromatin structure and transcriptional regulation of the 9p21 locus, including STAT1 binding, long-range enhancer interactions and expression of neighbouring genes.
- Olivier Harismendy
- , Dimple Notani
- & Kelly A. Frazer
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Letter |
S-glutathionylation uncouples eNOS and regulates its cellular and vascular function
The enzyme eNOS is crucial for regulating vascular function as it can produce both the vasodilator nitric oxide and the vasoconstrictor superoxide. Here it is shown that a modification associated with oxidant stress, S-glutathionylation, switches the enzyme from forming nitric oxide to forming superoxide. In hypertensive vessels, S-glutathionylation of eNOS is increased and this is associated with impaired endothelium-dependent vasodilation.
- Chun-An Chen
- , Tse-Yao Wang
- & Jay L. Zweier
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Article |
Biological, clinical and population relevance of 95 loci for blood lipids
Lipid concentration in the serum is one of the most important risk factors for coronary artery disease and can be targeted for therapeutic intervention. A genome-wide association study in >100,000 individuals of European ancestry now finds 95 significantly associated loci that also affect lipid traits in non-European populations. Among associated loci are those involved in cholesterol metabolism, known targets of cholesterol-lowering drugs and those that contribute to normal variation in lipid traits and to extreme lipid phenotypes.
- Tanya M. Teslovich
- , Kiran Musunuru
- & Sekar Kathiresan
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Research Highlights |
Cardiovascular biology: Low B cells, low plaques
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Letter |
Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice
Sequence variations in a 58-kilobase interval on human chromosome 9p21 have been associated with an increased risk of coronary artery disease. However, this interval contains no protein-coding genes and the mechanism underlying the increased risk has been unclear. Here, the corresponding interval has been deleted from mouse chromosome 4, revealing that this part of the chromosome regulates the cardiac expression of two nearby genes, Cdkn2a and Cdkn2b, and the proliferation dynamics of vascular cells.
- Axel Visel
- , Yiwen Zhu
- & Len A. Pennacchio
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News |
Junk DNA holds clues to heart disease
Deleting a non-coding region leads to narrowing of arteries in mice.
- Janet Fang
Convergence of coronary artery disease genes onto endothelial cell programs