Ischemic myocardial inflammatory signaling in starvation versus hypoxia-derived extracellular vesicles: A comparative analysisCentral MessagePerspective
Background: Coronary artery disease remains a leading cause of death worldwide. Bone mesenchymal stem cell–derived extracellular vesicles (EVs) have shown promise in the setting of myocardial ischemia. Furthermore, the properties of the EVs can be modified via preconditioning of progenitor cells. Pr...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | JTCVS Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666273623003169 |
| _version_ | 1797385000742551552 |
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| author | Mohamed Sabra, MD Sharif A. Sabe, MD Dwight D. Harris, MD Cynthia M. Xu, MD Mark Broadwin, MD Krishnah G. Bellam, BS Debolina Banerjee, MD M. Ruhul Abid, MD, PhD Frank W. Sellke, MD |
| author_facet | Mohamed Sabra, MD Sharif A. Sabe, MD Dwight D. Harris, MD Cynthia M. Xu, MD Mark Broadwin, MD Krishnah G. Bellam, BS Debolina Banerjee, MD M. Ruhul Abid, MD, PhD Frank W. Sellke, MD |
| author_sort | Mohamed Sabra, MD |
| collection | DOAJ |
| description | Background: Coronary artery disease remains a leading cause of death worldwide. Bone mesenchymal stem cell–derived extracellular vesicles (EVs) have shown promise in the setting of myocardial ischemia. Furthermore, the properties of the EVs can be modified via preconditioning of progenitor cells. Previous research from our lab demonstrated a significant decrease in proinflammatory signaling following treatment with EVs derived from starvation preconditioning of human bone mesenchymal stem cells (MVM EVs) in a porcine model of chronic myocardial ischemia. However, rodent models have demonstrated that the use of EVs derived from hypoxia preconditioning of bone mesenchymal stem cells (HYP EVs) may have extended benefits compared to MVM EVs. This study evaluated the effect of HYP EVs on inflammation in a swine model of chronic myocardial ischemia. We hypothesized that HYP EVs would have a greater anti-inflammatory effect than MVM EVs or saline (CON). Methods: Yorkshire swine fed a standard diet underwent placement of an ameroid constrictor to the left circumflex artery. Two weeks later, the animals received intramyocardial injection of saline (CON; n = 6), starvation-derived EVs (MVM; n = 10), or hypoxia-derived EVs (HYP; n = 7). After 5 weeks, myocardial perfusion was assessed, and left ventricular myocardial tissue was harvested. Protein expression was measured using immunoblotting. Data were analyzed via the Kruskal-Wallis test or one-way analysis of variance based on the results of a Shapiro-Wilk test. Coronary perfusion was plotted against relative cytokine concentration and analyzed with the Spearman rank-sum test. Results: HYP EV treatment was associated with decreased expression of proinflammatory markers interleukin (IL)-6 (P = .03), Pro-IL-1ß (P = .01), IL-17 (P < .01), and NOD-like receptor protein 3 (NLRP3; P < .01) compared to CON. Ischemic tissue from the MVM group showed significantly decreased expression of pro-inflammatory markers NLRP3 (P < .01), IL-17 (P < .01), and HLA class II histocompatibility antigen (P < .01) compared to CON. The MVM group also had decreased expression of anti-inflammatory IL-10 (P = .01) compared to CON counterparts. There were no significant differences in expression of tumor necrosis factor-α, interferon-γ, IL-12, Toll-like receptor-2, and nuclear factor kappa-light-chain-enhancer of activated B cells in either group . There was no correlation between coronary perfusion and cytokine concentration in the MVM or HYP groups, either at rest or with pacing. Conclusions: HYP EVs and MVM EVs appear to result in relative decreases in the degree of inflammation in chronically ischemic swine myocardium, independent of coronary perfusion. It is possible that this observed decrease may partially explain the myocardial benefits seen with both HYP and MVM EV treatment. |
| first_indexed | 2024-03-08T21:47:49Z |
| format | Article |
| id | doaj.art-1abe4224b2784819a9eb84c47a031940 |
| institution | Directory Open Access Journal |
| issn | 2666-2736 |
| language | English |
| last_indexed | 2024-03-08T21:47:49Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTCVS Open |
| spelling | doaj.art-1abe4224b2784819a9eb84c47a0319402023-12-20T07:38:23ZengElsevierJTCVS Open2666-27362023-12-0116419428Ischemic myocardial inflammatory signaling in starvation versus hypoxia-derived extracellular vesicles: A comparative analysisCentral MessagePerspectiveMohamed Sabra, MD0Sharif A. Sabe, MD1Dwight D. Harris, MD2Cynthia M. Xu, MD3Mark Broadwin, MD4Krishnah G. Bellam, BS5Debolina Banerjee, MD6M. Ruhul Abid, MD, PhD7Frank W. Sellke, MD8Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RIDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RIDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RIDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RIDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RIDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RIDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RIDivision of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RIAddress for reprints: Frank W. Sellke, MD, Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, 2 Dudley St, MOC 360, Providence, RI 02905.; Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RIBackground: Coronary artery disease remains a leading cause of death worldwide. Bone mesenchymal stem cell–derived extracellular vesicles (EVs) have shown promise in the setting of myocardial ischemia. Furthermore, the properties of the EVs can be modified via preconditioning of progenitor cells. Previous research from our lab demonstrated a significant decrease in proinflammatory signaling following treatment with EVs derived from starvation preconditioning of human bone mesenchymal stem cells (MVM EVs) in a porcine model of chronic myocardial ischemia. However, rodent models have demonstrated that the use of EVs derived from hypoxia preconditioning of bone mesenchymal stem cells (HYP EVs) may have extended benefits compared to MVM EVs. This study evaluated the effect of HYP EVs on inflammation in a swine model of chronic myocardial ischemia. We hypothesized that HYP EVs would have a greater anti-inflammatory effect than MVM EVs or saline (CON). Methods: Yorkshire swine fed a standard diet underwent placement of an ameroid constrictor to the left circumflex artery. Two weeks later, the animals received intramyocardial injection of saline (CON; n = 6), starvation-derived EVs (MVM; n = 10), or hypoxia-derived EVs (HYP; n = 7). After 5 weeks, myocardial perfusion was assessed, and left ventricular myocardial tissue was harvested. Protein expression was measured using immunoblotting. Data were analyzed via the Kruskal-Wallis test or one-way analysis of variance based on the results of a Shapiro-Wilk test. Coronary perfusion was plotted against relative cytokine concentration and analyzed with the Spearman rank-sum test. Results: HYP EV treatment was associated with decreased expression of proinflammatory markers interleukin (IL)-6 (P = .03), Pro-IL-1ß (P = .01), IL-17 (P < .01), and NOD-like receptor protein 3 (NLRP3; P < .01) compared to CON. Ischemic tissue from the MVM group showed significantly decreased expression of pro-inflammatory markers NLRP3 (P < .01), IL-17 (P < .01), and HLA class II histocompatibility antigen (P < .01) compared to CON. The MVM group also had decreased expression of anti-inflammatory IL-10 (P = .01) compared to CON counterparts. There were no significant differences in expression of tumor necrosis factor-α, interferon-γ, IL-12, Toll-like receptor-2, and nuclear factor kappa-light-chain-enhancer of activated B cells in either group . There was no correlation between coronary perfusion and cytokine concentration in the MVM or HYP groups, either at rest or with pacing. Conclusions: HYP EVs and MVM EVs appear to result in relative decreases in the degree of inflammation in chronically ischemic swine myocardium, independent of coronary perfusion. It is possible that this observed decrease may partially explain the myocardial benefits seen with both HYP and MVM EV treatment.http://www.sciencedirect.com/science/article/pii/S2666273623003169hypoxiaextracellular vesiclesmyocardial ischemiaswineameroidmyocardial inflammation |
| spellingShingle | Mohamed Sabra, MD Sharif A. Sabe, MD Dwight D. Harris, MD Cynthia M. Xu, MD Mark Broadwin, MD Krishnah G. Bellam, BS Debolina Banerjee, MD M. Ruhul Abid, MD, PhD Frank W. Sellke, MD Ischemic myocardial inflammatory signaling in starvation versus hypoxia-derived extracellular vesicles: A comparative analysisCentral MessagePerspective JTCVS Open hypoxia extracellular vesicles myocardial ischemia swine ameroid myocardial inflammation |
| title | Ischemic myocardial inflammatory signaling in starvation versus hypoxia-derived extracellular vesicles: A comparative analysisCentral MessagePerspective |
| title_full | Ischemic myocardial inflammatory signaling in starvation versus hypoxia-derived extracellular vesicles: A comparative analysisCentral MessagePerspective |
| title_fullStr | Ischemic myocardial inflammatory signaling in starvation versus hypoxia-derived extracellular vesicles: A comparative analysisCentral MessagePerspective |
| title_full_unstemmed | Ischemic myocardial inflammatory signaling in starvation versus hypoxia-derived extracellular vesicles: A comparative analysisCentral MessagePerspective |
| title_short | Ischemic myocardial inflammatory signaling in starvation versus hypoxia-derived extracellular vesicles: A comparative analysisCentral MessagePerspective |
| title_sort | ischemic myocardial inflammatory signaling in starvation versus hypoxia derived extracellular vesicles a comparative analysiscentral messageperspective |
| topic | hypoxia extracellular vesicles myocardial ischemia swine ameroid myocardial inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2666273623003169 |
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