Evidence map›Paper›PMID 24636283›Full record

ArticleThe journal of sexual medicine2014

Valproic acid prevents penile fibrosis and erectile dysfunction in cavernous nerve-injured rats.

Johanna L Hannan, Omer Kutlu, Bernard L Stopak, Xiaopu Liu, Fabio Castiglione, Petter Hedlund, Arthur L Burnett, Trinity J Bivalacqua

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The journal of sexual medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

26 citing papers in PubMed, 55 citations in OpenAlex.

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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

8 authors at 5 institutions in 4 countries.

Johanna L HannanDepartment of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Omer Kutlu
Bernard L Stopak
Xiaopu Liu
Fabio Castiglione
Petter Hedlund
Arthur L Burnett
Trinity J Bivalacqua
Johns Hopkins University · USJohns Hopkins Medicine · USKaradeniz Technical University · TRLinköping University · SESan Raffaele University of Rome · IT

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
Roles of RhoA/Rho-kinase Signaling in Cavernous Neurons Following Axonal InjuryK08DK090370 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI BIVALACQUA, TRINITY JUDE · 2011 to 2015
$794k
NCI NIH HHS P30 CA006973NIDDK NIH HHS K08DK090370
6 · The paper itself

Abstract

introductionBilateral cavernous nerve injury (BCNI) causes profound penile changes such as apoptosis and fibrosis leading to erectile dysfunction (ED). Histone deacetylase (HDAC) has been implicated in chronic fibrotic diseases.

aimsThis study will characterize the molecular changes in penile HDAC after BCNI and determine if HDAC inhibition can prevent BCNI-induced ED and penile fibrosis.

methodsFive groups of rats (8-10 weeks, n = 10/group) were utilized: (i) sham; (ii and iii) BCNI 14 and 30 days following injury; and (iv and v) BCNI treated with HDAC inhibitor valproic acid (VPA 250 mg/kg; 14 and 30 days). All groups underwent cavernous nerve stimulation (CNS) to determine intracavernosal pressure (ICP). Penile HDAC3, HDAC4, fibronectin, and transforming growth factor-β1 (TGF-β1) protein expression (Western blot) were assessed. Trichrome staining and the fractional area of fibrosis were determined in penes from each group. Cavernous smooth muscle content was assessed by immunofluorescence to alpha smooth muscle actin (α-SMA) antibodies.

main outcome measuresWe measured ICP; HDAC3, HDAC4, fibronectin, and TGF-β1 protein expression; penile fibrosis; penile α-SMA content.

resultsThere was a voltage-dependent decline (P < 0.05) in ICP to CNS 14 and 30 days after BCNI. Penile HDAC3, HDAC4, and fibronectin were significantly increased (P < 0.05) 14 days after BCNI. There was a slight increase in TGF-β1 protein expression after BCNI. Histological analysis showed increased (P < 0.05) corporal fibrosis after BCNI at both time points. VPA treatment decreased (P < 0.05) penile HDAC3, HDAC4, and fibronectin protein expression as well as corporal fibrosis. There was no change in penile α-SMA between all groups. Furthermore, VPA-treated BCNI rats had improved erectile responses to CNS (P < 0.05).

conclusionHDAC-induced pathological signaling in response to BCNI contributes to penile vascular dysfunction. Pharmacological inhibition of HDAC prevents penile fibrosis, normalizes fibronectin expression, and preserves erectile function. The HDAC pathway may represent a suitable target in preventing the progression of ED occurring post-radical prostatectomy.

Indexed as

AnimalsBlotting, WesternErectile DysfunctionFibrosisHistone Deacetylase InhibitorsHistone DeacetylasesMalePenile ErectionPenile IndurationPenisProstatectomyRats, Sprague-DawleySignal TransductionTransforming Growth Factor beta1Trauma, Nervous SystemValproic AcidHistone Deacetylase InhibitorsHistone DeacetylasesTransforming Growth Factor beta1Valproic AcidCavernous NerveErectile DysfunctionFactor BetaFibrosisHistone DeacetylaseTransforming Growth

Identifiers

PMID24636283
PMCPMC4048646
OpenAlexW2142643067

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.