Evidence map›Paper›PMID 26542693›Full record

ArticleStroke2015

Integrative Mouse and Human Studies Implicate ANGPT1 and ZBTB7C as Susceptibility Genes to Ischemic Injury.

Rose Du, Jing Zhou, Svetlana Lorenzano, Wenming Liu, Nareerat Charoenvimolphan, Baogang Qian, Jun Xu, Jian Wang, Xinmu Zhang, Xin Wang and 10 more

Open access · greenAbstract read
In one paragraph

Article in Stroke, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 24% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. The effect of angiopoietin-1 upregulation on the outcome of acute ischaemic stroke in rodent models: A meta-analysis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019
    Pooled it
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  4. Epigenetics communications · 2021
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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

20 authors at 8 institutions in 3 countries.

Rose DuFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.). rdu@partners.org.
Jing ZhouFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Svetlana LorenzanoFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Wenming LiuFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Nareerat CharoenvimolphanFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Baogang QianFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Jun XuFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Jian WangFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Xinmu ZhangFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Xin WangFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Annerose BerndtFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
William J DevanFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Valerie J ValantFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Jinyi WangFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Karen L FurieFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Jonathan RosandFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Natalia RostFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Robert M FriedlanderFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Beverly PaigenFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Scott T WeissFrom the Department of Neurosurgery (R.D., J.Z., W.L., N.C., B.Q., J.X., J.W., X.Z., X.W.) and Channing Division of Network Medicine, Department of Medicine (R.D., S.T.W.), Brigham and Women's Hospital, Boston, MA; Department of Neurology, Massachusetts General Hospital, Boston (S.L., W.J.D., V.J.V., J.R., N.R.); Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy (S.L.); Department of Chemical Biology, Northwest Agriculture and Forestry University, Shaanxi, People's Republic of China (W.L., J.W.); Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, People's Republic of China (J.X.); The Jackson Laboratory, Bar Harbor, ME (A.B., B.P.); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine (A.B.) and Department of Neurosurgery (R.M.F.), University of Pittsburgh School of Medicine, PA; Quinnipiac University Frank H. Netter, MD School of Medicine, Hamden, CT (W.J.D.); University of Massachusetts Medical School, Worcester (V.J.V.); and Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (K.L.F.).
Brown University · USSapienza University of Rome · ITUniversity of Massachusetts Chan Medical School · USUniversity of Pittsburgh · USChina-Japan Friendship Hospital · CNQuinnipiac University · USJackson Laboratory · USNorthwest A&F University · CN

Funding

Integrative Genomics of StrokeK08NS067172 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI DU, ROSE · 2009 to 2013
$924k
NINDS NIH HHS K08 NS067172NINDS NIH HHS K08NS067172
6 · The paper itself

Abstract

background and purposeThe extent of ischemic injury in response to cerebral ischemia is known to be affected by native vasculature. However, the nonvascular and dynamic vascular responses and their genetic basis are not well understood.

methodsWe performed a genome-wide association study in 235 mice from 33 inbred strains using the middle cerebral artery occlusion model. Population structure and genetic relatedness were accounted for using the efficient mixed-model association method. Human orthologs to the genes associated with the significant and suggestive single-nucleotide polymorphisms from the mouse strain survey were examined in patients with M1 occlusions admitted with signs and symptoms of acute ischemic stroke.

resultsWe identified 4 genome-wide significant and suggestive single-nucleotide polymorphisms to be associated with infarct volume in mice (rs3694965, P=2.17×10(-7); rs31924033, P=5.61×10(-6); rs32249495, P=2.08×10(-7); and rs3677406, P=9.56×10(-6)). rs32249495, which corresponds to angiopoietin-1 (ANGPT1), was also significant in the recessive model in humans, whereas rs1944577, which corresponds to ZBTB7C, was nominally significant in both the additive and dominant genetic models in humans. ZBTB7C was shown to be upregulated in endothelial cells using both in vitro and in vivo models of ischemia.

conclusionsGenetic variations of ANGPT1 and ZBTB7C are associated with increased infarct size in both mice and humans. ZBTB7C may modulate the ischemic response via neuronal apoptosis and dynamic collateralization and, in addition to ANGPT1, may serve as potential novel targets for treatments of cerebral ischemia.

Indexed as

Genome-Wide Association StudyAngiopoietin-1AnimalsBrain IschemiaFemaleGenetic Predisposition to DiseaseHumansIntracellular Signaling Peptides and ProteinsMaleMiceMice, 129 StrainMice, Inbred BALB CMice, Inbred C57BLMice, Inbred DBAMice, Inbred NODPolymorphism, Single NucleotideAngiopoietin-1ANGPT1 protein, humanIntracellular Signaling Peptides and ProteinsProteinsZBTB7C protein, humanbrain ischemiacerebral infarctiongeneticsmodels, animalstroke

Identifiers

PMID26542693
PMCPMC5704955
OpenAlexW2097146394

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