{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:49:51Z","timestamp":1773276591753,"version":"3.50.1"},"reference-count":26,"publisher":"Institute of Physiology of the Czech Academy of Sciences","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Dysfunction of pulmonary artery endothelial cells (PAECs) contributes to the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH). However, the role of mitochondrial metabolism in this process remains unclear. The present study evaluated whether the tetrameric form of pyruvate kinase muscle isoform 2 (PKM2) regulates PAEC mitochondrial metabolism through peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1\u03b1) and mitochondrial transcription factor A (mtTFA), thereby influencing arterial intimal remodeling in CTEPH. A CTEPH rat model was established by repeated injections of autologous thrombi. Activation of PKM2 tetramer expression was achieved through synthetic pyruvate kinase M2 activator (TEPP-46) administration. Pulmonary artery pressure (PAP), thrombus pathology, and protein expression levels of PKM2, mtTFA, and PGC-1\u03b1 were assessed. Plasma lactate concentrations and tumor necrosis factor alpha (TNF-\u03b1) levels were measured. Rats with CTEPH demonstrated thrombotic obstruction, elevated PAP, and reduced expression of the PKM2 tetramer, mtTFA, and PGC-1\u03b1. Treatment with TEPP-46 was associated with a reduction in thrombus burden, lower PAP, and restoration of mitochondrial protein expression, accompanied by decreased lactate concentrations and TNF-\u03b1 levels. In the CTEPH rat model, increased inflammation and elevated lactate concentrations were observed, along with decreased expression of mtTFA and PGC-1\u03b1 in the pulmonary artery intima, which is indicative of mitochondrial dysfunction. The PKM2 tetramer may play a role in modulating PAEC mitochondrial function, reducing pulmonary artery pressure, and improving pulmonary arterial intimal remodeling in CTEPH.<\/jats:p>","DOI":"10.33549\/physiolres.935691","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:37:55Z","timestamp":1773225475000},"page":"45","source":"Crossref","is-referenced-by-count":0,"title":["Role of PKM2 Tetramer in Modulating Endothelial Mitochondrial Dysfunction in a Rat Model of Chronic Thromboembolic Pulmonary Hypertension"],"prefix":"10.33549","author":[{"given":"M-X","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z-Z","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D-W","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M-H","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Q-X","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C-S","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"19169","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"1.\tHumbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, et al. 2022 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. 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