دورية أكاديمية
Hmgcs2 regulates M2 polarization of macrophages to repair myocardial injury induced by sepsis.
| العنوان: | Hmgcs2 regulates M2 polarization of macrophages to repair myocardial injury induced by sepsis. |
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| المؤلفون: | Zou XZ; Department of Critical Care Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning, PR China.; Department of Cardiovascular Surgery, General Hospital of Northern Theater Command of China Medical University, Laboratory of Rescue Center of Severe Wound and Trauma PLA, Shenyang 110016, Liaoning, PR China., Hao JF; Department of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, PR China., Hou MX; Department of Cardiovascular Surgery, General Hospital of Northern Theater Command of China Medical University, Laboratory of Rescue Center of Severe Wound and Trauma PLA, Shenyang 110016, Liaoning, PR China.; Shenyang Medical College, Shenyang 110034, Liaoning, PR China.; Department of Cardiovascular Surgery, The Second Affiliated Hospital of Shenyang Medical College, The Veterans General Hospital of Liaoning, Shenyang 110001, Liaoning, PR China. |
| المصدر: | Aging [Aging (Albany NY)] 2023 Aug 09; Vol. 15 (15), pp. 7794-7810. Date of Electronic Publication: 2023 Aug 09. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Impact Journals, LLC Country of Publication: United States NLM ID: 101508617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-4589 (Electronic) Linking ISSN: 19454589 NLM ISO Abbreviation: Aging (Albany NY) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Albany, NY : Impact Journals, LLC |
| مواضيع طبية MeSH: | Heart Injuries* , Sepsis*/metabolism, Mice ; Animals ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Mice, Inbred C57BL ; Macrophages/metabolism ; Myocytes, Cardiac/metabolism |
| مستخلص: | The respiratory and cardiovascular systems are often the most severely impacted by the rapid onset of sepsis, which can lead to multiple organ failure. The mortality has ranged from 10 to 40% when it has evolved into septic shock. This study sought to demonstrate the potential and role of Hmgcs2 in safeguarding against cardiovascular harm in septic mouse models. The cecal ligament and puncture (CLP) model was used to induce sepsis in C57BL/6 mice, with Hmgcs2 expression in the myocardium of the mice being heightened and inflammatory factors being augmented. Subsequently, we utilized ASOs to silence the hmgcs2 gene, and found that silencing accelerated septic myocardial injury and cardiac dysfunction in CLP mice models. In contrast, hmgcs2 attenuated inflammation and apoptosis and protected against septic cardiomyopathy in murine septicemia models. Src production, spurred on by Hmgcs2, triggered the PI3K/Akt pathway and augmented M2 macrophage polarization. Moreover, the inhibition of M2 polarization by an Src antagonist significantly contributed to apoptosis of cardiomyocytes. Our research revealed that Hmgcs2 inhibited the activation of pro-inflammatory macrophages and, through Src-dependent activation of PI3K/Akt pathway, promoted the anti-inflammatory phenotype, thus safeguarding myocardial damage from sepsis. This offers a novel theoretical basis for prevention and treatment of infectious complications. |
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| فهرسة مساهمة: | Keywords: CLP; Hmgcs2; M2; sepsis |
| المشرفين على المادة: | EC 2.7.1.- (Phosphatidylinositol 3-Kinases) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) |
| تواريخ الأحداث: | Date Created: 20230810 Date Completed: 20230822 Latest Revision: 20230827 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC10457052 |
| DOI: | 10.18632/aging.204944 |
| PMID: | 37561521 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-4589 |
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| DOI: | 10.18632/aging.204944 |