Evidence map›Paper›PMID 34241810›Full record

ArticleTranslational stroke research2022

Plasma Kallikrein Contributes to Intracerebral Hemorrhage and Hypertension in Stroke-Prone Spontaneously Hypertensive Rats.

Jian Guan, Allen C Clermont, Loc-Duyen Pham, Tuna Ustunkaya, Alexey S Revenko, A Robert MacLeod, Edward P Feener, Fabrício Simão

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

Article in Translational stroke research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. 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

8 authors at 4 institutions in 1 country.

Jian Guan *Research Division, Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA, 02215, USA.
Allen C Clermont *KalVista Pharmaceuticals, Inc., Cambridge, MA, USA.
Loc-Duyen PhamResearch Division, Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA, 02215, USA.
Tuna UstunkayaResearch Division, Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA, 02215, USA.
Alexey S RevenkoIonis Pharmaceuticals, Inc., Carlsbad, CA, USA.
A Robert MacLeodIonis Pharmaceuticals, Inc., Carlsbad, CA, USA.
Edward P FeenerKalVista Pharmaceuticals, Inc., Cambridge, MA, USA.
Fabrício SimãoResearch Division, Vascular Cell Biology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA, 02215, USA. Fabricio.simao@joslin.harvard.edu.
Joslin Diabetes Center · USIonis Pharmaceuticals (United States) · USKalVista Pharmaceuticals (United States) · USHarvard University · US

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Role of Hyperglycemia in Intracerebral HemorrhageR01NS077006 · NINDS · JOSLIN DIABETES CENTER · PI RASK-MADSEN, CHRISTIAN · 2012 to 2016
$1.8M
Role of bradykinin receptor 2 in tPA stroke therapyK01NS107798 · NINDS · JOSLIN DIABETES CENTER · PI SIMAO, FABRICIO · 2018 to 2020
$644k
NIDDK NIH HHS P30 DK036836NINDS NIH HHS K01 NS107798NINDS NIH HHS R01 NS077006
6 · The paper itself

Abstract

Plasma kallikrein (PKa) has been implicated in contributing to hemorrhage following thrombolytic therapy; however, its role in spontaneous intracerebral hemorrhage is currently not available. This report investigates the role of PKa on hemorrhage and hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were fed with a high salt-containing stroke-prone diet to increase blood pressure and induce intracerebral hemorrhage. The roles of PKa on blood pressure, hemorrhage, and survival in SHRSP were examined in rats receiving a PKa inhibitor or plasma prekallikrein antisense oligonucleotide (PK ASO) compared with rats receiving control ASO. Effects on PKa on the proteolytic cleavage of atrial natriuretic peptide (ANP) were analyzed by tandem mass spectrometry. We show that SHRSP on high-salt diet displayed increased levels of PKa activity compared with control rats. Cleaved kininogen was increased in plasma during stroke compared to SHRSP without stroke. Systemic administration of a PKa inhibitor or PK ASO to SHRSP reduced hemorrhage and blood pressure, and improved neurological function and survival compared with SHRSP receiving control ASO. Since PKa inhibition was associated with reduced blood pressure in hypertensive rats, we investigated the effects of PKa on the cleavage of ANP. Incubation of PKa with ANP resulted in the generation fragment ANP

Indexed as

HypertensionStrokeAnimalsAtrial Natriuretic FactorBlood PressureCerebral HemorrhagePlasma KallikreinRatsRats, Inbred SHRAtrial Natriuretic FactorPlasma KallikreinAtrial natriuretic peptideHypertensionIntracerebral hemorrhagePlasma kallikreinStroke

Identifiers

PMID34241810
PMCPMC8742844
OpenAlexW3178239757

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.