Role of Nitric Oxide in Cardioprotection by Poloxamer 188
Poloxamer (P) 188 attenuates myocardial ischemia/reperfusion injury through cell membrane stabilization. Cell–cell interactions between endothelial cells (ECs) and cardiomyocytes (CMs) further protect CMs: co-cultures showed that, at an optimal density, ECs protected CMs against hypoxia/reoxygenatio...
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MDPI AG
2025-06-01
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| author | Zhu Li Matthew B. Barajas Takuro Oyama Matthias L. Riess |
| author_facet | Zhu Li Matthew B. Barajas Takuro Oyama Matthias L. Riess |
| author_sort | Zhu Li |
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| description | Poloxamer (P) 188 attenuates myocardial ischemia/reperfusion injury through cell membrane stabilization. Cell–cell interactions between endothelial cells (ECs) and cardiomyocytes (CMs) further protect CMs: co-cultures showed that, at an optimal density, ECs protected CMs against hypoxia/reoxygenation (HR) injury. The mechanism of interaction with P188 still requires exploration. We examined if N(ω)-nitro-L-arginine methyl ester (LNAME), a non-specific nitric oxide (NO) synthase inhibitor, abolishes protection in the presence or absence of P188 and/or ECs. We co-cultured mouse coronary artery ECs in an insert atop mouse CMs plated at confluency on the bottom of a well. Normoxic controls remained in complete media while HR groups were exposed to 24 h hypoxia at 0.01% O<sub>2</sub> in serum- and glucose-free media, followed by 2 h reoxygenation in complete media. P188 (300 μM), LNAME (40 mM), or vehicle were administered upon reoxygenation. ECs at the used lower density did not decrease HR-triggered lactate dehydrogenase release or calcium overload in CMs by themselves. P188 reduced both indicators after HR by 16/18% without and by 22/25% with ECs, respectively. LNAME abrogated CM protection by P188. Neither intervention had an effect under normoxia. Our co-culture data indicates that P188 requires NO, not necessarily of endothelial origin, to elicit CM protection. |
| format | Article |
| id | doaj-art-288ad4cd413e4955a5585413dce49dbc |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-288ad4cd413e4955a5585413dce49dbc2025-08-20T03:28:25ZengMDPI AGCells2073-44092025-06-011413100110.3390/cells14131001Role of Nitric Oxide in Cardioprotection by Poloxamer 188Zhu Li0Matthew B. Barajas1Takuro Oyama2Matthias L. Riess3Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USAPoloxamer (P) 188 attenuates myocardial ischemia/reperfusion injury through cell membrane stabilization. Cell–cell interactions between endothelial cells (ECs) and cardiomyocytes (CMs) further protect CMs: co-cultures showed that, at an optimal density, ECs protected CMs against hypoxia/reoxygenation (HR) injury. The mechanism of interaction with P188 still requires exploration. We examined if N(ω)-nitro-L-arginine methyl ester (LNAME), a non-specific nitric oxide (NO) synthase inhibitor, abolishes protection in the presence or absence of P188 and/or ECs. We co-cultured mouse coronary artery ECs in an insert atop mouse CMs plated at confluency on the bottom of a well. Normoxic controls remained in complete media while HR groups were exposed to 24 h hypoxia at 0.01% O<sub>2</sub> in serum- and glucose-free media, followed by 2 h reoxygenation in complete media. P188 (300 μM), LNAME (40 mM), or vehicle were administered upon reoxygenation. ECs at the used lower density did not decrease HR-triggered lactate dehydrogenase release or calcium overload in CMs by themselves. P188 reduced both indicators after HR by 16/18% without and by 22/25% with ECs, respectively. LNAME abrogated CM protection by P188. Neither intervention had an effect under normoxia. Our co-culture data indicates that P188 requires NO, not necessarily of endothelial origin, to elicit CM protection.https://www.mdpi.com/2073-4409/14/13/1001calciumcardiomyocyteco-cultureco-polymercross-talkendothelium |
| spellingShingle | Zhu Li Matthew B. Barajas Takuro Oyama Matthias L. Riess Role of Nitric Oxide in Cardioprotection by Poloxamer 188 Cells calcium cardiomyocyte co-culture co-polymer cross-talk endothelium |
| title | Role of Nitric Oxide in Cardioprotection by Poloxamer 188 |
| title_full | Role of Nitric Oxide in Cardioprotection by Poloxamer 188 |
| title_fullStr | Role of Nitric Oxide in Cardioprotection by Poloxamer 188 |
| title_full_unstemmed | Role of Nitric Oxide in Cardioprotection by Poloxamer 188 |
| title_short | Role of Nitric Oxide in Cardioprotection by Poloxamer 188 |
| title_sort | role of nitric oxide in cardioprotection by poloxamer 188 |
| topic | calcium cardiomyocyte co-culture co-polymer cross-talk endothelium |
| url | https://www.mdpi.com/2073-4409/14/13/1001 |
| work_keys_str_mv | AT zhuli roleofnitricoxideincardioprotectionbypoloxamer188 AT matthewbbarajas roleofnitricoxideincardioprotectionbypoloxamer188 AT takurooyama roleofnitricoxideincardioprotectionbypoloxamer188 AT matthiaslriess roleofnitricoxideincardioprotectionbypoloxamer188 |