Evidence mapPaperPMID 39074126Full record

ArticlePloS one2024

Dipeptidyl peptidase 4 inhibitor sitagliptin decreases myocardial fibrosis and modulates myocardial insulin signaling in a swine model of chronic myocardial ischemia.

Dwight D Harris, Sharif A Sabe, Mark Broadwin, Chris Stone, Krishna Bellam, Akshay Malhotra, M Ruhul Abid, Frank W Sellke

Abstract read
In one paragraph

Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Dwight D HarrisDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, United States of America.ORCID https://orcid.org/0000-0001-8289-2740
Sharif A SabeDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, United States of America.ORCID https://orcid.org/0000-0002-8169-6753
Mark BroadwinDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, United States of America.
Chris StoneDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, United States of America.ORCID https://orcid.org/0000-0001-6457-2663
Krishna BellamDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, United States of America.ORCID https://orcid.org/0000-0001-9549-192X
Akshay MalhotraDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, United States of America.ORCID https://orcid.org/0000-0001-5047-6320
M Ruhul AbidDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, United States of America.ORCID https://orcid.org/0000-0003-2981-2638
Frank W SellkeDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, United States of America.

Funding

CARDIOPLEGIA AND CORONARY MICROVASCULAR REACTIVITYR01HL046716 · BETH ISRAEL DEACONESS MEDICAL CENTER · 1997 to 2004
$1.5M
Vascular Dysfunction in Myocardial Ischemia and Metabolic SyndromeR01HL128831 · RHODE ISLAND HOSPITAL · 2025 to 2025
$818k
Cardiovascular Surgery Research TrainingT32HL160517 · RHODE ISLAND HOSPITAL · 2025 to 2025
$338k
NHLBI NIH HHS R01 HL046716NHLBI NIH HHS R01 HL128831NHLBI NIH HHS T32 HL160517
6 · The paper itself

Abstract

Although both clinical data and animal models suggest cardiovascular benefits following administration of Dipeptidyl Peptidase 4 (DPP-4) inhibitors, the underlying mechanisms remain unclear. We therefore sought to evaluate the effect of the DPP-4 inhibitor sitagliptin on myocardial fibrosis, and insulin signaling in chronic myocardial ischemia using a swine model. An ameroid constrictor placement on the left coronary circumflex artery of thirteen Yorkshire swine to model chronic myocardial ischemia. After two weeks of recovery, swine were assigned to one of two groups: control (CON, n = 8), or sitagliptin 100mg daily (SIT, n = 5). After 5 weeks of treatment, the swine underwent terminal harvest with collection of myocardial tissue. Fibrosis was quantified using Masson's trichrome. Protein expression was quantified by Immunoblotting. Trichrome stain demonstrated a significant decrease in perivascular and interstitial fibrosis in the SIT group relative to CON (all p<0.05). Immunoblot showed a reduction in Jak2, the pSTAT3 to STAT 3 Ratio, pSMAD 2/3, and SMAD 2/3, and an increase in STAT 3 in the SIT group relative to CON (all p<0.05). SIT treatment was associated with increased expression of insulin receptor one and decreased expression of makers for insulin resistance, including phospho-PKC- alpha, RBP-4, SIRT1, and PI3K (p<0.05). Sitagliptin results in a reduction in perivascular and interstitial fibrosis and increased insulin sensitivity in chronically ischemic swine myocardium. This likely contributes to the improved cardiovascular outcomes seen with DPP-4 inhibitors.

Indexed as

Dipeptidyl-Peptidase IV InhibitorsDisease Models, AnimalFibrosisInsulinMyocardial IschemiaMyocardiumSignal TransductionSitagliptin PhosphateAnimalsChronic DiseaseSwineDipeptidyl-Peptidase IV InhibitorsInsulinSitagliptin Phosphate

Identifiers

PMID39074126
PMCPMC11285952

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.