Tirzepatide Attenuates Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension: Association with the SIRT1/H4K12la/c-Jun Axis.

Sutong Zhan, Yong Deng, Peilin Chen, Tangfeng Lv, Yong Song, Jiaxin Liu, Chuiyu Kong

Abstract read

In one paragraph

Article in Cells, 2026. 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

7 authors.

Sutong ZhanDepartment of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, China.

Yong DengDepartment of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China.

Peilin ChenDepartment of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, China.

Tangfeng LvDepartment of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, China.

Yong SongDepartment of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, China.

Jiaxin LiuDepartment of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China.ORCID 0000-0002-7048-1992

Chuiyu KongDepartment of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China.ORCID 0009-0000-2259-3351

Funding

National Natural Science Foundation of China 82403837

6 · The paper itself

Abstract

Metabolic reprogramming and the phenotypic switching of pulmonary arterial smooth muscle cells (PASMCs) are critical pathological features of pulmonary arterial hypertension (PAH). Here, we demonstrated that Tirzepatide (TZP) can significantly ameliorate echocardiographic indicators of pulmonary vascular load and attenuate distal pulmonary vascular remodeling by suppressing PASMC phenotypic switching. Metabolomics and cellular metabolic flux analyses revealed that TZP corrected the Warburg effect, thereby attenuating intracellular lactate accumulation, which we identified as a driver that promotes the synthetic phenotype in PASMCs and exacerbates PAH. Mechanistically, the protective effects of TZP were strongly associated with the activation of the AMPK/SIRT1 signaling pathway, which mediated a significant reduction in histone H4 lysine 12 lactylation (H4K12la). This epigenetic reduction suppressed the transcription of the proto-oncogene

Indexed as

HistonesProto-Oncogene Proteins c-junPulmonary Arterial HypertensionSirtuin 1TirzepatideVascular RemodelingAMP-Activated Protein KinasesAnimalsHumansMaleMyocytes, Smooth MuscleProto-Oncogene MasPulmonary ArterySignal TransductionAMP-Activated Protein KinasesHistonesProto-Oncogene MasProto-Oncogene Proteins c-junSirtuin 1Tirzepatidehistone lactylationmetabolic reprogrammingphenotypic switchingpulmonary arterial hypertensiontirzepatide

Identifiers

PMID42929872

DOI10.3390/cells15201900

PMCPMC13702887

What OpenQuestion holds

Textmetadata

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.