Evidence map›Paper›PMID 32160775›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2020

Sickle Cell Anemia Mediates Carotid Artery Expansive Remodeling That Can Be Prevented by Inhibition of JNK (c-Jun N-Terminal Kinase).

Hannah Song, Philip M Keegan, Suhaas Anbazhakan, Christian P Rivera, Yundi Feng, Victor O Omojola, Alexus A Clark, Shuangyi Cai, Jada Selma, Rudolph L Gleason and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Cerebral arteries in mice with sickle cell disease are exposed to larger areas of low wall shear stress.American journal of physiology. Heart and circulatory physiology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Microfluidic methods to advance mechanistic understanding and translational research in sickle cell disease.Translational research : the journal of laboratory and clinical medicine · 2022
    Review
  8. Article
  9. Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Hannah SongFrom the Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta (H.S., P.M.K., S.A., C.P.R., V.O.O., A.A.C., S.C., J.S., R.L.G., E.A.B., M.O.P.).
Philip M KeeganFrom the Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta (H.S., P.M.K., S.A., C.P.R., V.O.O., A.A.C., S.C., J.S., R.L.G., E.A.B., M.O.P.).
Suhaas AnbazhakanFrom the Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta (H.S., P.M.K., S.A., C.P.R., V.O.O., A.A.C., S.C., J.S., R.L.G., E.A.B., M.O.P.).
Christian P RiveraFrom the Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta (H.S., P.M.K., S.A., C.P.R., V.O.O., A.A.C., S.C., J.S., R.L.G., E.A.B., M.O.P.).
Yundi FengDepartment of Mechanics and Engineering Science at Peking University, Beijing, China (C.P.R., Y.F., Y.H., W.T.).
Victor O OmojolaFrom the Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta (H.S., P.M.K., S.A., C.P.R., V.O.O., A.A.C., S.C., J.S., R.L.G., E.A.B., M.O.P.).
Alexus A ClarkFrom the Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta (H.S., P.M.K., S.A., C.P.R., V.O.O., A.A.C., S.C., J.S., R.L.G., E.A.B., M.O.P.).
Shuangyi CaiFrom the Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta (H.S., P.M.K., S.A., C.P.R., V.O.O., A.A.C., S.C., J.S., R.L.G., E.A.B., M.O.P.).
Jada SelmaFrom the Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta (H.S., P.M.K., S.A., C.P.R., V.O.O., A.A.C., S.C., J.S., R.L.G., E.A.B., M.O.P.).
Rudolph L GleasonFrom the Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta (H.S., P.M.K., S.A., C.P.R., V.O.O., A.A.C., S.C., J.S., R.L.G., E.A.B., M.O.P.).
Edward A BotchweyFrom the Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta (H.S., P.M.K., S.A., C.P.R., V.O.O., A.A.C., S.C., J.S., R.L.G., E.A.B., M.O.P.).
Yunlong HuoDepartment of Mechanics and Engineering Science at Peking University, Beijing, China (C.P.R., Y.F., Y.H., W.T.).
Wenchang TanDepartment of Mechanics and Engineering Science at Peking University, Beijing, China (C.P.R., Y.F., Y.H., W.T.).
Manu O PlattFrom the Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta (H.S., P.M.K., S.A., C.P.R., V.O.O., A.A.C., S.C., J.S., R.L.G., E.A.B., M.O.P.).
Georgia Institute of Technology · USPeking University · CNThe Wallace H. Coulter Department of Biomedical Engineering · US

Funding

Multiscale, mechanistic, and predictive models of stroke in sickle cell diseaseDP2OD007433 · OD · GEORGIA INSTITUTE OF TECHNOLOGY · PI PLATT, MANU O · 2010 to 2010
$2.3M
Proteolytic mechanisms of arterial remodeling and strokes in sickle cell diseaseR56HL136210 · NHLBI · GEORGIA INSTITUTE OF TECHNOLOGY · PI PLATT, MANU O · 2017 to 2017
$511k
NHLBI NIH HHS R56 HL136210NIH HHS DP2 OD007433
6 · The paper itself

Abstract

objectiveSickle cell anemia (SCA) causes chronic inflammation and multiorgan damage. Less understood are the arterial complications, most evident by increased strokes among children. Proteolytic mechanisms, biomechanical consequences, and pharmaceutical inhibitory strategies were studied in a mouse model to provide a platform for mechanistic and intervention studies of large artery damage due to sickle cell disease. Approach and Results: Townes humanized transgenic mouse model of SCA was used to test the hypothesis that elastic lamina and structural damage in carotid arteries increased with age and was accelerated in mice homozygous for SCA (sickle cell anemia homozygous genotype [SS]) due to inflammatory signaling pathways activating proteolytic enzymes. Elastic lamina fragmentation observed by 1 month in SS mice compared with heterozygous littermate controls (sickle cell trait heterozygous genotype [AS]). Positive immunostaining for cathepsin K, a powerful collagenase and elastase, confirmed accelerated proteolytic activity in SS carotids. Larger cross-sectional areas were quantified by magnetic resonance angiography and increased arterial compliance in SS carotids were also measured. Inhibiting JNK (c-jun N-terminal kinase) signaling with SP600125 significantly reduced cathepsin K expression, elastin fragmentation, and carotid artery perimeters in SS mice. By 5 months of age, continued medial thinning and collagen degradation was mitigated by treatment of SS mice with JNK inhibitor.

conclusionsArterial remodeling due to SCA is mediated by JNK signaling, cathepsin proteolytic upregulation, and degradation of elastin and collagen. Demonstration in Townes mice establishes their utility for mechanistic studies of arterial vasculopathy, related complications, and therapeutic interventions for large artery damage due to SCA.

Indexed as

Anemia, Sickle CellAnimalsAnthracenesCarotid ArteriesCarotid Artery DiseasesCathepsin KCollagenDisease Models, AnimalElastinHemoglobinsHomozygoteHumansJNK Mitogen-Activated Protein KinasesMice, TransgenicMutationProtein Kinase InhibitorsAnthracenesCathepsin KCollagenCtsk protein, mouseElastinHemoglobinsJNK Mitogen-Activated Protein KinasesProtein Kinase Inhibitorspyrazolanthronecarotid arteriescollagencomplianceelastinhematology

Identifiers

PMID32160775
PMCPMC7224328
OpenAlexW3012131076

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.