HomeCirculation: Heart FailureVol. 15, No. 8Letter by Li and Nie Regarding Article, “Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Li and Nie Regarding Article, “Inflammatory Glycoprotein 130 Signaling Links Changes in Microtubules and Junctophilin-2 to Altered Mitochondrial Metabolism and Right Ventricular Contractility” Ruopu Li, MD, PhD and Yu Nie, PhD Ruopu LiRuopu Li https://orcid.org/0000-0002-7724-018X State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for more papers by this author and Yu NieYu Nie https://orcid.org/0000-0002-8744-0046 State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for more papers by this author Originally published27 Jun 2022https://doi.org/10.1161/CIRCHEARTFAILURE.122.009531Circulation: Heart Failure. 2022;15Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: June 27, 2022: Ahead of Print To the Editor:We read with great interest the recent article by Prisco et al1 regarding the cardiac-protective role of gp130 blockade in monocrotaline induced pulmonary artery hypertension reflected by the antihypertrophy, antifibrotic effect, and the mitigated right ventricle function after gp130 antagonist SC-144 administration. The study expanded our consideration of gp130’s downstream signal to right heart function and its connecting role of inflammation, cytoskeleton organization and energy metabolism. However, here are some questions we would like to raise regarding the findings in the original article.Regenerative repair after myocardial injury requires gp130-induced STAT3 and Src-YAP pathways.2,3 And it has been reported that the loss of gp130 signaling in heart lead to adaption incapacity under biomechanical stress of pressure overload.4 We would like to respectfully ask what is the authors’ perspective on the opposite biological effect of gp130 concerning cardiac tissue response toward stress between left and right ventricle.Although major, there are different pathways downstream of gp130 other than Jak-STAT3. Did the author also detect other signaling pathways, including Erk-MAPK (extracellular regulated protein kinases-mitogen activated protein kinase pathway), PI3K-Akt (phosphoinositide-3 kinase-serine/threonine kinase Akt [also known as protein kinase B or PKB] pathway), and Src-YAP (pathway of proto-oncogene tyrosine-protein kinase Src and its downstream protein Yes associated protein [YAP]) pathways, in the pulmonary artery hypertension model before and after SC-144 administration? And did the author confirm the similar effect with SC-144 treatment under STAT3 antagonized model? SC-144 was adopted for the construction of gp130 depletion model. But the agent triggers different gp130 downstream signaling alteration including STAT3 inhibition and Erk activation.5The author treated immortalized H9c2 cell line with cytoskeleton stabilizer paclitaxel and detected an impaired mitochondrial metabolic activity. Here, we expected whether cytoskeleton interference would result in the same outcome in mitochondrial metabolism in primary neonatal rat ventricular myocytes (primary cardiomyocytes isolated form neonatal Rattus norvegicus). Paclitaxel has cytotoxicity on proliferative cells by inhibiting spindle formation, and cell mitosis is an energy-consuming process. So, the impair of cell cycle results in metabolic dysfunction. It is confusing whether it was due to the cell cycle toxicity or the cytoskeleton stabilizing that causes the alteration of mitochondrial metabolism.Article InformationSources of FundingThis work was supported by the National Natural Science Foundation of China (grant 81970243) and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (grant 2021-I2M-1-008).Disclosures None.FootnotesFor Sources of Funding and Disclosures, see page 823.
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