GEO series
Role of Pdk4 in BAPN-induecd aortic dissection in mouse models
GSE314672
Homo sapiens; Mus musculus
Expression profiling by high throughput sequencing
39 samples
Submitted 2026/03/27
Platform GPL24676Platform GPL24247
Summary
Thoracic aortic dissection (TAD) is a life-threatening acute vascular condition with extremely high morbidity and mortality. Endothelial cells (ECs) are critical for maintaining vascular homeostasis, yet the role of Endothelial-to-Mesenchymal Transition (EndoMT)—a key cell fate process in vascular development and disease—in TAD remains poorly defined. Furthermore, the functional significance of EndoMT-gene-program activation mediated by pyruvate dehydrogenase kinase 4 (PDK4) in TAD has not been elucidated. To explore the mechanistic involvement of EndoMT in TAD, a murine TAD model was established through systemic administration of β-aminopropionitrile (BAPN). RNA sequencing was performed to profile the activation landscape of the EndoMT-gene-program in ECs for identifying key regulatory targets. Concurrently, clinical samples from TAD patients and healthy controls were analyzed to quantify mRNA and protein levels of EndoMT-related markers in aortic tissues. Pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) was identified as a critical regulator and validated as a downstream target of EndoMT signaling using an integrated approach combining RNA-seq, luciferase reporter assays, and immunofluorescent staining. The functional role of Pdk4 in TAD was further validated by using conditional knockout (CKO) mouse model. To facilitate better clinical translation, EC-specific Pdk4 deletion or overexpression mouse models were generated via adeno-associated virus (AAV)-mediated delivery and subjected to TAD model. Serum samples from these mice were collected, and enzyme-linked immunosorbent assay (ELISA) was used to measure levels of endothelial injury markers (sICAM1, sVCAM1, sE-Selectin) for assessing endothelial dysfunction. Additionally, the therapeutic potential of dichloroacetate (DCA), a specific PDK4 inhibitor, was evaluated by administering it to BAPN-fed mice to assess its efficacy in ameliorating TAD progression. A significant upregulation of the EndoMT-gene-program was observed in BAPN-fed murine models of TAD, aortic tissues from TAD patients, and HAECs treated with angiotensin II (Ang II). Administration of AAVEndoPdk4 directly induced TAD formation, which was exacerbated by BAPN co-treatment. Conversely, EC-specific knockdown of Pdk4 reduced TAD formation by inhibiting EndoMT signaling. The same results were also obtained in EC-specific conditional Pdk4 knockout mice (CKO, Pdk4flox/flox; Cdh5-CreERT2). PDK4 was identified as a critical factor in both TAD development and EndoMT process, with SNAI1 transcriptionally activating PDK4; vice versa, PDK4 further enhanced the activation of EndoMT signaling in both in vivo and vitro. PDK4 inhibitor, DCA, significantly slowed TAD progression in BAPN-fed mice. Mechanistically, a PDK4-EndoMT feedback loop was identified in TAD, where interruption of this self-reinforcing pathological cycle markedly attenuates the progression of TAD.
Published in
Cao X, Guo X, Huang H et al.
· Arteriosclerosis, thrombosis, and vascular biology 2026
· PMID 41853864
· doi:10.1161/ATVBAHA.125.324031
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE314672_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 39 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1392438 and SRA study SRP657254. Searching any of these in the dataset finder brings you back here.
Study design
13 conditions, mostly in triplicate
Aorta, BAPN_Control, ×3
Aorta, BAPN_Week2, ×3
Aorta, BAPN_Week4, ×3
Aorta, KD_Pdk4_Saline, ×3
Aorta, KD_Pdk4_BAPN, ×3
Aorta, KD_CTR_Saline, ×3
Aorta, KD_CTR_BAPN, ×3
Cells, OE_Scramble, ×3
+5 more
Supports a between-group comparison across 39 samples.
13 replicated groups read from 39 sample titles; they account for 39 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9409030 Aorta, BAPN_Control, R1
- GSM9409031 Aorta, BAPN_Control, R2
- GSM9409032 Aorta, BAPN_Control, R3
- GSM9409033 Aorta, BAPN_Week2, R1
- GSM9409034 Aorta, BAPN_Week2, R2
- GSM9409035 Aorta, BAPN_Week2, R3
- GSM9409036 Aorta, BAPN_Week4, R1
- GSM9409037 Aorta, BAPN_Week4, R2
- GSM9409038 Aorta, BAPN_Week4, R3
- GSM9409039 Aorta, KD_Pdk4_Saline, R1
- GSM9409040 Aorta, KD_Pdk4_Saline, R2
- GSM9409041 Aorta, KD_Pdk4_Saline, R3
- GSM9409042 Aorta, KD_Pdk4_BAPN, R1
- GSM9409043 Aorta, KD_Pdk4_BAPN, R2
- GSM9409044 Aorta, KD_Pdk4_BAPN, R3
- GSM9409045 Aorta, KD_CTR_Saline, R1
- GSM9409046 Aorta, KD_CTR_Saline, R2
- GSM9409047 Aorta, KD_CTR_Saline, R3
- GSM9409048 Aorta, KD_CTR_BAPN, R1
- GSM9409049 Aorta, KD_CTR_BAPN, R2
- GSM9409050 Aorta, KD_CTR_BAPN, R3
- GSM9409051 Cells, OE_Scramble, R1
- GSM9409052 Cells, OE_Scramble, R2
- GSM9409053 Cells, OE_Scramble, R3
- GSM9409054 Cells, OE_PDK4, R1
- GSM9409055 Cells, OE_PDK4, R2
- GSM9409056 Cells, OE_PDK4, R3
- GSM9409057 Aorta, OE_CTR_Saline, R1
- GSM9409058 Aorta, OE_CTR_Saline, R2
- GSM9409059 Aorta, OE_CTR_Saline, R3
- GSM9409060 Aorta, OE_CTR_BAPN, R1
- GSM9409061 Aorta, OE_CTR_BAPN, R2
- GSM9409062 Aorta, OE_CTR_BAPN, R3
- GSM9409063 Aorta, OE_Pdk4_BAPN, R1
- GSM9409064 Aorta, OE_Pdk4_BAPN, R2
- GSM9409065 Aorta, OE_Pdk4_BAPN, R3
- GSM9409066 Aorta, OE_Pdk4_Saline, R1
- GSM9409067 Aorta, OE_Pdk4_Saline, R2
- GSM9409068 Aorta, OE_Pdk4_Saline, R3
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