Pub Date : 2024-09-25DOI: 10.1016/j.niox.2024.09.009
Xutong Sun , Santiago Moreno Caceres , Manivannan Yegambaram , Qing Lu , Marissa D. Pokharel , Jason T. Boehme , Sanjeev A. Datar , Saurabh Aggarwal , Ting Wang , Jeffrey R. Fineman , Stephen M. Black
Previously, we have shown that endothelial nitric-oxide synthase (eNOS) dimer levels directly correlate with the interaction of eNOS with hsp90 (heat shock protein 90). Further, the disruption of eNOS dimerization correlates with its redistribution to the mitochondria. However, the causal link between these events has yet to be investigated and was the focus of this study. Our data demonstrates that simvastatin, which decreases the mitochondrial redistribution of eNOS, increased eNOS-hsp90 interactions and enhanced eNOS dimerization in cultured pulmonary arterial endothelial cells (PAEC) from a lamb model of pulmonary hypertension (PH). Our data also show that the dimerization of a monomeric fraction of human recombinant eNOS was stimulated in the presence of hsp90 and ATP. The over-expression of a dominant negative mutant of hsp90 (DNHsp90) decreased eNOS dimer levels and enhanced its mitochondrial redistribution. We also found that the peroxynitrite donor3-morpholinosydnonimine (SIN-1) increased the mitochondrial redistribution of eNOS in PAEC and this was again associated with decreased eNOS dimer levels. Our data also show in COS-7 cells, the SIN-1 mediated mitochondrial redistribution of wildtype eNOS (WT-eNOS) is significantly higher than a dimer stable eNOS mutant protein (C94R/C99R-eNOS). Conversely, the mitochondrial redistribution of a monomeric eNOS mutant protein (C96A-eNOS) was enhanced. Finally, we linked the SIN-1-mediated mitochondrial redistribution of eNOS to the Akt1-mediated phosphorylation of eNOS at Serine(S)617 and showed that the accessibility of this residue to phosphorylation is regulated by dimerization status. Thus, our data reveal a novel mechanism of pulmonary endothelial dysfunction mediated by mitochondrial redistribution of eNOS, regulated by dimerization status and the phosphorylation of S617.
{"title":"The mitochondrial redistribution of ENOS is regulated by AKT1 and dimer status","authors":"Xutong Sun , Santiago Moreno Caceres , Manivannan Yegambaram , Qing Lu , Marissa D. Pokharel , Jason T. Boehme , Sanjeev A. Datar , Saurabh Aggarwal , Ting Wang , Jeffrey R. Fineman , Stephen M. Black","doi":"10.1016/j.niox.2024.09.009","DOIUrl":"10.1016/j.niox.2024.09.009","url":null,"abstract":"<div><div>Previously, we have shown that endothelial nitric-oxide synthase (eNOS) dimer levels directly correlate with the interaction of eNOS with hsp90 (heat shock protein 90). Further, the disruption of eNOS dimerization correlates with its redistribution to the mitochondria. However, the causal link between these events has yet to be investigated and was the focus of this study. Our data demonstrates that simvastatin, which decreases the mitochondrial redistribution of eNOS, increased eNOS-hsp90 interactions and enhanced eNOS dimerization in cultured pulmonary arterial endothelial cells (PAEC) from a lamb model of pulmonary hypertension (PH). Our data also show that the dimerization of a monomeric fraction of human recombinant eNOS was stimulated in the presence of hsp90 and ATP. The over-expression of a dominant negative mutant of hsp90 (DNHsp90) decreased eNOS dimer levels and enhanced its mitochondrial redistribution. We also found that the peroxynitrite donor3-morpholinosydnonimine (SIN-1) increased the mitochondrial redistribution of eNOS in PAEC and this was again associated with decreased eNOS dimer levels. Our data also show in COS-7 cells, the SIN-1 mediated mitochondrial redistribution of wildtype eNOS (WT-eNOS) is significantly higher than a dimer stable eNOS mutant protein (C94R/C99R-eNOS). Conversely, the mitochondrial redistribution of a monomeric eNOS mutant protein (C96A-eNOS) was enhanced. Finally, we linked the SIN-1-mediated mitochondrial redistribution of eNOS to the Akt1-mediated phosphorylation of eNOS at Serine(S)<sup>617</sup> and showed that the accessibility of this residue to phosphorylation is regulated by dimerization status. Thus, our data reveal a novel mechanism of pulmonary endothelial dysfunction mediated by mitochondrial redistribution of eNOS, regulated by dimerization status and the phosphorylation of S<sup>617</sup>.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/j.niox.2024.09.008
Nevra Alkanli , Arzu Ay , Gokhan Cevik
<div><h3>Background</h3><div>This study aimed to investigate the relationships between eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations and prostate cancer development and progression.</div></div><div><h3>Materials and methods</h3><div>This study included 88 patients diagnosed with prostate cancer and 91 healthy controls. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were used to determine the genotype distributions of eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations.</div></div><div><h3>Results</h3><div>In our study, the CC homozygous genotype of eNOS T786C gene variation was determined to be significantly higher in the prostate cancer patient group compared to the healthy control group (OR: 2.343, 95%Cl: 0.990–5.544, p = 0.026), while the CT heterozygous genotype was found to be significantly higher in the healthy control group compared to the prostate cancer patient group was found to be significantly higher (OR: 0.589, 95%Cl: 0.325–1.068, p = 0.041). In addition, while the TT homozygous genotype of the eNOS G894T gene variation was found to be significantly higher in the prostate cancer patient group compared to the healthy control group (OR: 9.068, 95%Cl: 4.396–18.777, p < 0.001), the GT heterozygous genotype was found to be significantly higher in the healthy control group compared to the prostate cancer patient group was determined significantly higher (OR: 0.227, 95%Cl: 0.121–0.427, p < 0.001). For eNOS (4VNTR (4a/b) - G894T) gene variations, aa-TT (p = 0.042) and bb-TT (p < 0.001) haplotype frequencies were significantly higher in the prostate cancer patient group, while aa-GT (p = 0.017), bb-GG (p = 0.049) and bb-GT (p < 0.001) haplotype frequencies were found to be significantly higher in the healthy control group. For eNOS (4VNTR (4a/b) - T786C) gene variations, the bb-CC haplotype frequency was determined to be significantly higher in the patient group (p = 0.049), while the bb-CT haplotype frequency was determined to be significantly higher in the control group (p = 0.008). For eNOS (T786C -G894T) gene variations, TT-TT (p < 0.001) and CC-TT (p = 0.025) haplotype frequencies were found to be significantly higher in the patient group. On the other hand, TT-GT (p = 0.002) and CT-GT (p < 0.001) haplotype frequencies were determined to be significantly higher in the control group. The aa genotype of the intron 4 VNTR (4a/b) gene variation was determined to be significantly higher at Gleason score ≥7 compared to Gleason score <7 (OR: 0.184, 95%Cl: 0.050–0.677, p = 0.005). PSA levels were determined significantly higher in patients with Gleason score 7 and above (p = 0.008). The risk of developing prostate cancer was found to be significantly higher in patients carrying the CC homozygous mutant genotype of the eNOS T786C gene variation (p = 0.024) and in patients carrying the TT homozygous genotype of the G894T gene variation (p = 0.021).</div></div><div><h3>
{"title":"Investigation of the relationships between eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations and prostate cancer development and progression","authors":"Nevra Alkanli , Arzu Ay , Gokhan Cevik","doi":"10.1016/j.niox.2024.09.008","DOIUrl":"10.1016/j.niox.2024.09.008","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to investigate the relationships between eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations and prostate cancer development and progression.</div></div><div><h3>Materials and methods</h3><div>This study included 88 patients diagnosed with prostate cancer and 91 healthy controls. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were used to determine the genotype distributions of eNOS T786C, G894T, intron 4 VNTR (4a/b) gene variations.</div></div><div><h3>Results</h3><div>In our study, the CC homozygous genotype of eNOS T786C gene variation was determined to be significantly higher in the prostate cancer patient group compared to the healthy control group (OR: 2.343, 95%Cl: 0.990–5.544, p = 0.026), while the CT heterozygous genotype was found to be significantly higher in the healthy control group compared to the prostate cancer patient group was found to be significantly higher (OR: 0.589, 95%Cl: 0.325–1.068, p = 0.041). In addition, while the TT homozygous genotype of the eNOS G894T gene variation was found to be significantly higher in the prostate cancer patient group compared to the healthy control group (OR: 9.068, 95%Cl: 4.396–18.777, p < 0.001), the GT heterozygous genotype was found to be significantly higher in the healthy control group compared to the prostate cancer patient group was determined significantly higher (OR: 0.227, 95%Cl: 0.121–0.427, p < 0.001). For eNOS (4VNTR (4a/b) - G894T) gene variations, aa-TT (p = 0.042) and bb-TT (p < 0.001) haplotype frequencies were significantly higher in the prostate cancer patient group, while aa-GT (p = 0.017), bb-GG (p = 0.049) and bb-GT (p < 0.001) haplotype frequencies were found to be significantly higher in the healthy control group. For eNOS (4VNTR (4a/b) - T786C) gene variations, the bb-CC haplotype frequency was determined to be significantly higher in the patient group (p = 0.049), while the bb-CT haplotype frequency was determined to be significantly higher in the control group (p = 0.008). For eNOS (T786C -G894T) gene variations, TT-TT (p < 0.001) and CC-TT (p = 0.025) haplotype frequencies were found to be significantly higher in the patient group. On the other hand, TT-GT (p = 0.002) and CT-GT (p < 0.001) haplotype frequencies were determined to be significantly higher in the control group. The aa genotype of the intron 4 VNTR (4a/b) gene variation was determined to be significantly higher at Gleason score ≥7 compared to Gleason score <7 (OR: 0.184, 95%Cl: 0.050–0.677, p = 0.005). PSA levels were determined significantly higher in patients with Gleason score 7 and above (p = 0.008). The risk of developing prostate cancer was found to be significantly higher in patients carrying the CC homozygous mutant genotype of the eNOS T786C gene variation (p = 0.024) and in patients carrying the TT homozygous genotype of the G894T gene variation (p = 0.021).</div></div><div><h3>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-21DOI: 10.1016/j.niox.2024.09.007
Jia Shi , Yuhua Liu , Shuxiang Jiao , Tao Wu , Ai Wang , Wenming Wang , Leilei Xie , Yanhong Liu , Hongfei Wang
Four isomeric nitrosyl ruthenium complexes [RuCl(2mqn)(Val)(NO)] (1–4) were prepared (2mqn, 2-methyl-8-hydroxyquinoline; Val, l-valine) and characterized by 1H NMR, 13C NMR, absorption spectrum, electrospray ionization mass spectrometry, and X-ray crystal diffraction. Time-resolved FT-IR and fluorescence spectroscopy were used to monitor photo-induced NO release in solution, while NO released in living cells was imaged using a selective fluorescent probe. The isomeric complexes showed different levels of cytotoxicity against HeLa cells, and slightly photo-enhanced anti-proliferative activity was observed. The isomeric complexes 1–4 inhibited the growth of HeLa cells by inducing apoptosis and promoted cell cycle arrest in the S phase. Furthermore, they showed relatively lower cytotoxicity against the human liver cell line HL-7702. The different spatial configurations of the complexes is close related with the selective binding of the isomeric complexes with serum albumin, which provide insight into the potential applications of the nitrosyl ruthenium complexes.
制备了四种异构亚硝基钌配合物[RuCl(2mqn)(Val)(NO)]（1-4）（2mqn，2-甲基-8-羟基喹啉；Val，L-缬氨酸），并通过 1H NMR、13C NMR、吸收光谱、电喷雾离子化质谱和 X 射线晶体衍射进行了表征。利用时间分辨傅立叶变换红外光谱和荧光光谱监测溶液中光诱导的 NO 释放，同时利用选择性荧光探针对活细胞中释放的 NO 进行成像。异构体复合物对 HeLa 细胞表现出不同程度的细胞毒性，并观察到轻微的光增强抗增殖活性。异构复合物 1-4 通过诱导细胞凋亡抑制了 HeLa 细胞的生长，并促进细胞周期停滞在 S 期。此外，它们对人类肝细胞系 HL-7702 的细胞毒性相对较低。复合物的不同空间构型与异构复合物与血清白蛋白的选择性结合密切相关，这为亚硝基钌复合物的潜在应用提供了启示。
{"title":"Synthesis, structure, spectra, cytotoxicity and photo induced NO release of four isomeric nitrosylruthenium complexes","authors":"Jia Shi , Yuhua Liu , Shuxiang Jiao , Tao Wu , Ai Wang , Wenming Wang , Leilei Xie , Yanhong Liu , Hongfei Wang","doi":"10.1016/j.niox.2024.09.007","DOIUrl":"10.1016/j.niox.2024.09.007","url":null,"abstract":"<div><div>Four isomeric nitrosyl ruthenium complexes [RuCl(2mqn)(Val)(NO)] (<strong>1</strong>–<strong>4</strong>) were prepared (2mqn, 2-methyl-8-hydroxyquinoline; Val, <span>l</span>-valine) and characterized by <sup>1</sup>H NMR, <sup>13</sup>C NMR, absorption spectrum, electrospray ionization mass spectrometry, and X-ray crystal diffraction. Time-resolved FT-IR and fluorescence spectroscopy were used to monitor photo-induced NO release in solution, while NO released in living cells was imaged using a selective fluorescent probe. The isomeric complexes showed different levels of cytotoxicity against HeLa cells, and slightly photo-enhanced anti-proliferative activity was observed. The isomeric complexes <strong>1</strong>–<strong>4</strong> inhibited the growth of HeLa cells by inducing apoptosis and promoted cell cycle arrest in the S phase. Furthermore, they showed relatively lower cytotoxicity against the human liver cell line HL-7702. The different spatial configurations of the complexes is close related with the selective binding of the isomeric complexes with serum albumin, which provide insight into the potential applications of the nitrosyl ruthenium complexes.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.niox.2024.09.005
Xiaoming Fu , Haowei Lu , Meng Gao , Pinghe Li , Yan He , Yu He , Xiaojian Luo , Xiaoyong Rao , Wei Liu
Nitric oxide (NO) plays a crucial role as a messenger or effector in the body, yet it presents a dual impact on cardio-cerebrovascular health. Under normal physiological conditions, NO exhibits vasodilatory effects, regulates blood pressure, inhibits platelet aggregation, and offers neuroprotective actions. However, in pathological situations, excessive NO production contributes to or worsens inflammation within the body. Moreover, NO may combine with reactive oxygen species (ROS), generating harmful substances that intensify physical harm. This paper succinctly reviews pertinent literature to clarify the in vivo and in vitro origins of NO, its regulatory function in the cardio-cerebrovascular system, and the advantages and disadvantages associated with NO donor drugs, NO delivery systems, and vascular stent materials for treating cardio-cerebrovascular disease. The findings provide a theoretical foundation for the application of NO in cardio-cerebrovascular diseases.
一氧化氮（NO）在人体内扮演着信使或效应器的重要角色，但它对心脑血管健康具有双重影响。在正常生理条件下，一氧化氮具有扩张血管、调节血压、抑制血小板聚集和保护神经的作用。然而，在病理情况下，过量的 NO 会导致或加剧体内炎症。此外，一氧化氮还可能与活性氧（ROS）结合，产生有害物质，加剧对身体的伤害。本文简明扼要地回顾了相关文献，阐明了 NO 在体内和体外的起源、在心脑血管系统中的调节功能，以及治疗心脑血管疾病的 NO 供体药物、NO 输送系统和血管支架材料的优缺点。研究结果为 NO 在心脑血管疾病中的应用提供了理论基础。
{"title":"Nitric oxide in the cardio-cerebrovascular system: Source, regulation and application","authors":"Xiaoming Fu , Haowei Lu , Meng Gao , Pinghe Li , Yan He , Yu He , Xiaojian Luo , Xiaoyong Rao , Wei Liu","doi":"10.1016/j.niox.2024.09.005","DOIUrl":"10.1016/j.niox.2024.09.005","url":null,"abstract":"<div><div>Nitric oxide (NO) plays a crucial role as a messenger or effector in the body, yet it presents a dual impact on cardio-cerebrovascular health. Under normal physiological conditions, NO exhibits vasodilatory effects, regulates blood pressure, inhibits platelet aggregation, and offers neuroprotective actions. However, in pathological situations, excessive NO production contributes to or worsens inflammation within the body. Moreover, NO may combine with reactive oxygen species (ROS), generating harmful substances that intensify physical harm. This paper succinctly reviews pertinent literature to clarify the in vivo and in vitro origins of NO, its regulatory function in the cardio-cerebrovascular system, and the advantages and disadvantages associated with NO donor drugs, NO delivery systems, and vascular stent materials for treating cardio-cerebrovascular disease. The findings provide a theoretical foundation for the application of NO in cardio-cerebrovascular diseases.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.niox.2024.09.006
Yuanqin Zhao , Yanxia Wang , Hongyu Zheng , Qian Xu , Kun Zhou , Huiting Liu , Yu Xia , Dang-Heng Wei , Miao Jiang , Zhi-Han Tang , Lu-Shan Liu , He Zheng , Zhisheng Jiang
<div><h3>Background</h3><div>Under normal circumstances, high-density lipoprotein (HDL) is considered to have cardiovascular protective effects, but the impact of oxidized HDL (ox-HDL) on vascular endothelial function remains poorly understood. Mitochondrial function is closely related to endothelial function, and hydrogen sulfide (H₂S) is a gas with endothelial protective properties. The novel hydrogen sulfide donor AP39 can target mitochondria to release H₂S, but the combined effects of ox-HDL and AP39 on vascular endothelium are not well studied.</div></div><div><h3>Methods</h3><div>We established a cell model of ox-HDL-induced endothelial cell damage and mitochondrial dysfunction using human umbilical vein endothelial cells (HUVECs) and conducted AP39 pretreatment. The experiments confirmed the functional damage and mitochondrial dysfunction in HUVECs caused by ox-HDL. Additionally, to further explore the role of SIRT1 in AS, we analyzed SIRT1 expression in AS carotid artery tissue. This included the analysis of differentially expressed genes from AS-related datasets, presented through volcano plots and heatmaps, with enrichment analysis of downregulated genes in KEGG pathways and GO functions. Furthermore, we evaluated the differences in SIRT1 expression in coronary arteries with varying degrees of stenosis and in early and late-stage AS carotid artery tissues, and analyzed data from SIRT1 knockout mouse models.</div></div><div><h3>Results</h3><div>The experimental results indicate that AP39 effectively alleviated ox-HDL-induced endothelial cell damage and mitochondrial dysfunction by upregulating SIRT1 expression. MTT and CCK-8 assays showed that ox-HDL treatment led to decreased cell viability and proliferation in HUVECs, reduced eNOS expression, and significantly increased levels of ICAM-1, IL-6, and TNF-α, along with enhanced monocyte adhesion. These findings reveal the damaging effects of ox-HDL on HUVECs. Transcriptomic data indicated that while SIRT1 expression did not significantly differ in coronary arteries with varying degrees of stenosis, it was notably downregulated in AS carotid artery tissues, especially in late-stage AS tissues. KEGG pathway enrichment analysis revealed that SIRT1 downregulated genes were associated with processes such as vascular smooth muscle contraction, while GO analysis showed that these downregulated genes were involved in muscle system processes and muscle contraction functions, further confirming SIRT1's critical role in AS pathology. In transcriptomic data from the SIRT1 knockout mouse model, elevated levels of inflammation-related proteins IL-6 and TNF-α were observed after SIRT1 knockout, along with decreased expression of the chaperone protein PGC-1α. The expression of mitochondrial-related functional proteins Nrf2 and PGC-1α was positively correlated with SIRT1 expression, while inflammation-related proteins ICAM-1, IL-6, IL-20, and TNF-α were negatively correlated with SIRT1 expression. We furth
{"title":"Hydrogen sulfide upregulates SIRT1 to inhibit ox-HDL-induced endothelial cell damage and mitochondrial dysfunction","authors":"Yuanqin Zhao , Yanxia Wang , Hongyu Zheng , Qian Xu , Kun Zhou , Huiting Liu , Yu Xia , Dang-Heng Wei , Miao Jiang , Zhi-Han Tang , Lu-Shan Liu , He Zheng , Zhisheng Jiang","doi":"10.1016/j.niox.2024.09.006","DOIUrl":"10.1016/j.niox.2024.09.006","url":null,"abstract":"<div><h3>Background</h3><div>Under normal circumstances, high-density lipoprotein (HDL) is considered to have cardiovascular protective effects, but the impact of oxidized HDL (ox-HDL) on vascular endothelial function remains poorly understood. Mitochondrial function is closely related to endothelial function, and hydrogen sulfide (H₂S) is a gas with endothelial protective properties. The novel hydrogen sulfide donor AP39 can target mitochondria to release H₂S, but the combined effects of ox-HDL and AP39 on vascular endothelium are not well studied.</div></div><div><h3>Methods</h3><div>We established a cell model of ox-HDL-induced endothelial cell damage and mitochondrial dysfunction using human umbilical vein endothelial cells (HUVECs) and conducted AP39 pretreatment. The experiments confirmed the functional damage and mitochondrial dysfunction in HUVECs caused by ox-HDL. Additionally, to further explore the role of SIRT1 in AS, we analyzed SIRT1 expression in AS carotid artery tissue. This included the analysis of differentially expressed genes from AS-related datasets, presented through volcano plots and heatmaps, with enrichment analysis of downregulated genes in KEGG pathways and GO functions. Furthermore, we evaluated the differences in SIRT1 expression in coronary arteries with varying degrees of stenosis and in early and late-stage AS carotid artery tissues, and analyzed data from SIRT1 knockout mouse models.</div></div><div><h3>Results</h3><div>The experimental results indicate that AP39 effectively alleviated ox-HDL-induced endothelial cell damage and mitochondrial dysfunction by upregulating SIRT1 expression. MTT and CCK-8 assays showed that ox-HDL treatment led to decreased cell viability and proliferation in HUVECs, reduced eNOS expression, and significantly increased levels of ICAM-1, IL-6, and TNF-α, along with enhanced monocyte adhesion. These findings reveal the damaging effects of ox-HDL on HUVECs. Transcriptomic data indicated that while SIRT1 expression did not significantly differ in coronary arteries with varying degrees of stenosis, it was notably downregulated in AS carotid artery tissues, especially in late-stage AS tissues. KEGG pathway enrichment analysis revealed that SIRT1 downregulated genes were associated with processes such as vascular smooth muscle contraction, while GO analysis showed that these downregulated genes were involved in muscle system processes and muscle contraction functions, further confirming SIRT1's critical role in AS pathology. In transcriptomic data from the SIRT1 knockout mouse model, elevated levels of inflammation-related proteins IL-6 and TNF-α were observed after SIRT1 knockout, along with decreased expression of the chaperone protein PGC-1α. The expression of mitochondrial-related functional proteins Nrf2 and PGC-1α was positively correlated with SIRT1 expression, while inflammation-related proteins ICAM-1, IL-6, IL-20, and TNF-α were negatively correlated with SIRT1 expression. We furth","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The biochemical interplay between antioxidants and pro-oxidants maintains the redox homeostatic balance of the cell, which, when perturbed to moderate or high extents, has been implicated in the onset and/or progression of chronic diseases such as diabetes mellitus, cancer, and neurodegenerative diseases. Thioredoxin, glutaredoxin, and lipoic acid-like thiol oxidoreductase systems constitute a unique ensemble of robust cellular antioxidant defenses, owing to their indispensable roles as S-denitrosylases, S-deglutathionylases, and disulfide reductants in maintaining a reduced free thiol state with biological relevance. Thus, in cells subjected to nitrosative stress, cellular antioxidants will S-denitrosylate their cognate S-nitrosoprotein substrates, rather than participate in trans-S-nitrosylation via protein-protein interactions. Researchers have been at the forefront of vaguely establishing the concept of ‘transnitrosylation’ and its influence on pathophysiology with experimental evidence from in vitro studies that lack proper biochemical logic. The suggestive and reiterative use of antioxidants as transnitrosylases in the scientific literature leaves us on a cliffhanger with several open-ended questions that prompted us to ‘hunt’ for scientific logic behind the trans-S-nitrosylation chemistry. Given the gravity of the situation and to look at the bigger picture of ‘trans-S-nitrosylation’, we aim to present a novel attempt at justifying the hesitance in accepting antioxidants as capable of transnitrosylating their cognate protein partners and reflecting on the need to resolve the controversy that would be crucial from the perspective of understanding therapeutic outcomes involving such cellular antioxidants in disease pathogenesis. Further characterization is required to identify the regulatory mechanisms or conditions where an antioxidant like Trx, Grx, or DJ-1 can act as a cellular transnitrosylase.
{"title":"The hunt for transnitrosylase","authors":"Surupa Chakraborty, Ankita Choudhuri , Akansha Mishra , Rajib Sengupta","doi":"10.1016/j.niox.2024.09.004","DOIUrl":"10.1016/j.niox.2024.09.004","url":null,"abstract":"<div><div>The biochemical interplay between antioxidants and pro-oxidants maintains the redox homeostatic balance of the cell, which, when perturbed to moderate or high extents, has been implicated in the onset and/or progression of chronic diseases such as diabetes mellitus, cancer, and neurodegenerative diseases. Thioredoxin, glutaredoxin, and lipoic acid-like thiol oxidoreductase systems constitute a unique ensemble of robust cellular antioxidant defenses, owing to their indispensable roles as S-denitrosylases, S-deglutathionylases, and disulfide reductants in maintaining a reduced free thiol state with biological relevance. Thus, in cells subjected to nitrosative stress, cellular antioxidants will S-denitrosylate their cognate S-nitrosoprotein substrates, rather than participate in <em>trans</em>-S-nitrosylation <em>via</em> protein-protein interactions. Researchers have been at the forefront of vaguely establishing the concept of ‘transnitrosylation’ and its influence on pathophysiology with experimental evidence from <em>in vitro</em> studies that lack proper biochemical logic. The suggestive and reiterative use of antioxidants as transnitrosylases in the scientific literature leaves us on a cliffhanger with several open-ended questions that prompted us to ‘hunt’ for scientific logic behind the <em>trans</em>-S-nitrosylation chemistry. Given the gravity of the situation and to look at the bigger picture of ‘<em>trans</em>-S-nitrosylation’, we aim to present a novel attempt at justifying the hesitance in accepting antioxidants as capable of transnitrosylating their cognate protein partners and reflecting on the need to resolve the controversy that would be crucial from the perspective of understanding therapeutic outcomes involving such cellular antioxidants in disease pathogenesis. Further characterization is required to identify the regulatory mechanisms or conditions where an antioxidant like Trx, Grx, or DJ-1 can act as a cellular transnitrosylase.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1016/j.niox.2024.09.002
Mi-Rong Jing , Xiao-Yi Liang , Yan-Xia Zhang , Yi-Wen Zhu , Yan Wang , Ti Chu , Yu-Qing Jin , Chuan-Hao Zhang , Shuai-Gang Zhu , Chao-Jing Zhang , Qi-Meng Wang , Zhi-Fen Feng , Xin-Ying Ji , Dong-Dong Wu
The mutual regulation between hydrogen sulfide (H2S) and microRNA (miRNA) is involved in the development of many diseases, including cancer, cardiovascular disease, inflammatory disease, and high-risk pregnancy. Abnormal expressions of endogenous H2S-producing enzyme and miRNA in tissues and cells often indicate the occurrence of diseases, so the maintenance of their normal levels in the body can mitigate damages caused by various factors. Many studies have found that H2S can promote the migration, invasion, and proliferation of cancer cells by regulating the expression of miRNA, while many H2S donors can inhibit cancer progression by interfering with the proliferation, apoptosis, cell cycle, metastasis, and angiogenesis of cancer cells. Furthermore, the mutual regulation between H2S and miRNA can also prevent cell injury in cardiovascular disease and inflammatory disease through anti-inflammation, anti-oxidation, anti-apoptosis, and pro-autophagy. In addition, H2S can promote angiogenesis and relieve vasoconstriction by regulating the expression of miRNA, thereby improving fetal growth in high-risk pregnancy. In this review, we discuss the mechanism of mutual regulation between H2S and miRNA in various diseases, which may provide reliable therapeutic targets for these diseases.
{"title":"Role of hydrogen sulfide-microRNA crosstalk in health and disease","authors":"Mi-Rong Jing , Xiao-Yi Liang , Yan-Xia Zhang , Yi-Wen Zhu , Yan Wang , Ti Chu , Yu-Qing Jin , Chuan-Hao Zhang , Shuai-Gang Zhu , Chao-Jing Zhang , Qi-Meng Wang , Zhi-Fen Feng , Xin-Ying Ji , Dong-Dong Wu","doi":"10.1016/j.niox.2024.09.002","DOIUrl":"10.1016/j.niox.2024.09.002","url":null,"abstract":"<div><div>The mutual regulation between hydrogen sulfide (H<sub>2</sub>S) and microRNA (miRNA) is involved in the development of many diseases, including cancer, cardiovascular disease, inflammatory disease, and high-risk pregnancy. Abnormal expressions of endogenous H<sub>2</sub>S-producing enzyme and miRNA in tissues and cells often indicate the occurrence of diseases, so the maintenance of their normal levels in the body can mitigate damages caused by various factors. Many studies have found that H<sub>2</sub>S can promote the migration, invasion, and proliferation of cancer cells by regulating the expression of miRNA, while many H<sub>2</sub>S donors can inhibit cancer progression by interfering with the proliferation, apoptosis, cell cycle, metastasis, and angiogenesis of cancer cells. Furthermore, the mutual regulation between H<sub>2</sub>S and miRNA can also prevent cell injury in cardiovascular disease and inflammatory disease through anti-inflammation, anti-oxidation, anti-apoptosis, and pro-autophagy. In addition, H<sub>2</sub>S can promote angiogenesis and relieve vasoconstriction by regulating the expression of miRNA, thereby improving fetal growth in high-risk pregnancy. In this review, we discuss the mechanism of mutual regulation between H<sub>2</sub>S and miRNA in various diseases, which may provide reliable therapeutic targets for these diseases.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1016/j.niox.2024.09.003
Chengqing Song , Qian Chen , Jiao Xu , Kaichuan He , Qi Guo , Xu Teng , Hongmei Xue , Lin Xiao , Danyang Tian , Sheng Jin , Cuixia An , Yuming Wu
To investigate the protective mechanisms of hydrogen sulfide (H2S) in sepsis-induced acute kidney injury (SAKI), we conducted an in vivo study using a SAKI mouse model induced by intraperitoneal lipopolysaccharide (LPS) injection. Following 6 h of LPS injection, levels of tumor necrosis factor-alpha (TNF-α) and blood urea nitrogen (Bun) were significantly elevated in mouse plasma. In the kidneys of SAKI mice, expression of H2S-generating enzymes cysteinyl-tRNA synthetase (CARS), cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) was markedly downregulated, while glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phosphorylated protein kinase R-like endoplasmic reticulum kinase/protein kinase R-like endoplasmic reticulum kinase (p-PERK/PERK), and B-cell lymphoma-2 recombinant protein X/B-cell lymphoma-2 (Bax/Bcl2) expression was significantly upregulated. H2S improved renal function and attenuated renal histopathological changes in SAKI mice, thereby alleviating LPS-induced endoplasmic reticulum stress (ERS). Additionally, it inhibited the expression of p-PERK/PERK and Bax/Bcl2. After inhibiting CSE activity with dl-propargylglycine (PPG i. p.), the renal tissue pathology in LPS-induced AKI mice was further exacerbated, leading to enhanced activation of the PERK/Bax-Bcl2 pathway. Our findings suggest that endogenous H2S influences the pathogenesis of SAKI, while exogenous H2S protects against LPS-induced AKI by inhibiting the PERK/Bax-Bcl2 pathway involved in ERS.
为了研究硫化氢（H2S）在脓毒症诱导的急性肾损伤（SAKI）中的保护机制，我们使用腹腔注射脂多糖（LPS）诱导的 SAKI 小鼠模型进行了一项体内研究。注射 LPS 6 小时后，小鼠血浆中肿瘤坏死因子-α（TNF-α）和血尿素氮（Bun）的水平显著升高。在 SAKI 小鼠的肾脏中，H2S 生成酶半胱氨酰-tRNA 合成酶（CARS）、胱硫醚γ-赖氨酸酶（CSE）和胱硫醚β-合成酶（CBS）的表达明显下调，而葡萄糖调节蛋白 78（GRP78）、活化转录因子 6（ATF6）、磷酸化蛋白激酶 Rl（PKRl）、胱硫醚γ-赖氨酸酶（CSE）和胱硫醚β-合成酶（CBS）的表达明显下降、磷酸化蛋白激酶 R 样内质网激酶/蛋白激酶 R 样内质网激酶（p-PERK/PERK）和 B 细胞淋巴瘤-2 重组蛋白 X/B细胞淋巴瘤-2（Bax/Bcl2）的表达则显著上调。H2S 改善了 SAKI 小鼠的肾功能，减轻了肾组织病理学变化，从而缓解了 LPS 诱导的内质网应激（ERS）。此外，它还抑制了 p-PERK/PERK 和 Bax/Bcl2 的表达。用 dl-丙炔基甘氨酸（PPG i. p.）抑制 CSE 活性后，LPS 诱导的 AKI 小鼠肾组织病理变化进一步加剧，导致 PERK/Bax-Bcl2 通路激活增强。我们的研究结果表明，内源性 H2S 会影响 SAKI 的发病机制，而外源性 H2S 可通过抑制参与 ERS 的 PERK/Bax-Bcl2 通路来防止 LPS 诱导的 AKI。
{"title":"H2S alleviated sepsis-induced acute kidney injury by inhibiting PERK/Bax-Bcl2 pathway","authors":"Chengqing Song , Qian Chen , Jiao Xu , Kaichuan He , Qi Guo , Xu Teng , Hongmei Xue , Lin Xiao , Danyang Tian , Sheng Jin , Cuixia An , Yuming Wu","doi":"10.1016/j.niox.2024.09.003","DOIUrl":"10.1016/j.niox.2024.09.003","url":null,"abstract":"<div><p>To investigate the protective mechanisms of hydrogen sulfide (H<sub>2</sub>S) in sepsis-induced acute kidney injury (SAKI), we conducted an in vivo study using a SAKI mouse model induced by intraperitoneal lipopolysaccharide (LPS) injection. Following 6 h of LPS injection, levels of tumor necrosis factor-alpha (TNF-α) and blood urea nitrogen (Bun) were significantly elevated in mouse plasma. In the kidneys of SAKI mice, expression of H<sub>2</sub>S-generating enzymes cysteinyl-tRNA synthetase (CARS), cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) was markedly downregulated, while glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phosphorylated protein kinase R-like endoplasmic reticulum kinase/protein kinase R-like endoplasmic reticulum kinase (p-PERK/PERK), and B-cell lymphoma-2 recombinant protein X/B-cell lymphoma-2 (Bax/Bcl2) expression was significantly upregulated. H<sub>2</sub>S improved renal function and attenuated renal histopathological changes in SAKI mice, thereby alleviating LPS-induced endoplasmic reticulum stress (ERS). Additionally, it inhibited the expression of p-PERK/PERK and Bax/Bcl2. After inhibiting CSE activity with <span>dl</span>-propargylglycine (PPG i. p.), the renal tissue pathology in LPS-induced AKI mice was further exacerbated, leading to enhanced activation of the PERK/Bax-Bcl2 pathway. Our findings suggest that endogenous H<sub>2</sub>S influences the pathogenesis of SAKI, while exogenous H<sub>2</sub>S protects against LPS-induced AKI by inhibiting the PERK/Bax-Bcl2 pathway involved in ERS.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1016/j.niox.2024.09.001
Tejasvi Pandey , Vivek Pandey
Hydrogen sulfide (H2S) has emerged as a potent therapeutic agent with diverse physiological functions, including vasodilation, anti-inflammation, and cytoprotection. However, its clinical application is limited due to its volatility and potential toxicity at high concentrations. To address these challenges, researchers have developed various H2S prodrugs that release H2S in a controlled and targeted manner. The review underscores the importance of targeting and delivery strategies in maximizing the therapeutic potential of H2S, a gasotransmitter with diverse physiological functions and therapeutic effects. By summarizing recent advancements, the review provides valuable insights for researchers and clinicians interested in harnessing the therapeutic benefits of H2S while minimizing off-target effects and toxicity. The integration of novel targeting and delivery approaches not only enhances the efficacy of H2S-based therapeutics but also expands the scope of potential applications, offering promising avenues for the development of new treatments for a variety of diseases and disorders.
{"title":"Advancements in increasing efficiency of hydrogen sulfide in therapeutics: Strategies for targeted delivery as prodrugs","authors":"Tejasvi Pandey , Vivek Pandey","doi":"10.1016/j.niox.2024.09.001","DOIUrl":"10.1016/j.niox.2024.09.001","url":null,"abstract":"<div><p>Hydrogen sulfide (H2S) has emerged as a potent therapeutic agent with diverse physiological functions, including vasodilation, anti-inflammation, and cytoprotection. However, its clinical application is limited due to its volatility and potential toxicity at high concentrations. To address these challenges, researchers have developed various H2S prodrugs that release H2S in a controlled and targeted manner. The review underscores the importance of targeting and delivery strategies in maximizing the therapeutic potential of H2S, a gasotransmitter with diverse physiological functions and therapeutic effects. By summarizing recent advancements, the review provides valuable insights for researchers and clinicians interested in harnessing the therapeutic benefits of H2S while minimizing off-target effects and toxicity. The integration of novel targeting and delivery approaches not only enhances the efficacy of H2S-based therapeutics but also expands the scope of potential applications, offering promising avenues for the development of new treatments for a variety of diseases and disorders.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.1016/j.niox.2024.08.003
Magdalena Litman , Neil J. Spratt , Daniel J. Beard
Background
Nitroglycerin has been of considerable interest as a treatment for ischaemic stroke. Recent clinical trials with nitroglycerin transdermal patches during the acute phase of stroke failed to improve functional outcomes. Systematic review and meta-analysis of the effectiveness of nitroglycerin in preclinical models of ischaemic stroke has not previously been reported, despite several clinical trials.
Objective
To conduct a systematic review and meta-analysis of preclinical evidence regarding the effect of nitroglycerin on infarct volume in animal models of ischaemic stroke.
Summary of review
The protocol was registered in PROSPERO (CRD42023432644). Our search identified 238 publications. Three publications met inclusion criteria (including 10 comparisons of infarct size). Study quality was modest (median 6 out of 9), with no evidence of publication bias. Nitroglycerin did not significantly reduce infarct volume (NMD point estimate 20.2 % reduction, 95 % CI −1.52–52.7 %, p = 0.068). Subgroup analysis suggested greater efficacy of nitroglycerin with direct intracarotid administration to the ischaemic territory at the time of reperfusion.
Conclusions
A small number of studies (three) were included in this review. Overall, nitroglycerin did not reduce infarct volume in experimental stroke models. However, nitroglycerin may be of benefit when administered directly into the ischaemic territory. Given nitroglycerin's short half-life, we propose this route may minimise harmful reduction of cerebral perfusion pressure resulting from hypotension following systemic administration.
背景：硝酸甘油作为缺血性中风的治疗药物一直备受关注。最近在中风急性期使用硝酸甘油透皮贴剂的临床试验未能改善功能预后。尽管有几项临床试验，但关于硝酸甘油在缺血性中风临床前模型中有效性的系统综述和荟萃分析此前尚未见报道：目的：对有关硝酸甘油对缺血性中风动物模型梗死体积影响的临床前证据进行系统综述和荟萃分析：该方案已在 PROSPERO（CRD42023432644）上注册。我们的检索发现了 238 篇文献。三篇文献符合纳入标准（包括 10 项梗死面积比较）。研究质量一般（中位数为 6（满分 9 分）），没有证据表明存在发表偏倚。硝酸甘油不能显著减少梗死体积（NMD 点估计值减少 20.2%，95% CI -1.52-52.7%, p = 0.068）。亚组分析表明，在再灌注时直接在缺血区域进行颈动脉内给药的硝酸甘油疗效更好：本综述纳入了少量研究（三项）。总体而言，硝酸甘油并未减少实验性中风模型的梗死体积。然而，硝酸甘油直接进入缺血区域可能有益。鉴于硝酸甘油的半衰期较短，我们认为这一途径可将全身给药后低血压导致的脑灌注压降低的危害降至最低。
{"title":"The effect of nitroglycerin treatment on cerebral ischaemia: A systematic review and meta-analysis of animal studies","authors":"Magdalena Litman , Neil J. Spratt , Daniel J. Beard","doi":"10.1016/j.niox.2024.08.003","DOIUrl":"10.1016/j.niox.2024.08.003","url":null,"abstract":"<div><h3>Background</h3><p>Nitroglycerin has been of considerable interest as a treatment for ischaemic stroke. Recent clinical trials with nitroglycerin transdermal patches during the acute phase of stroke failed to improve functional outcomes. Systematic review and meta-analysis of the effectiveness of nitroglycerin in preclinical models of ischaemic stroke has not previously been reported, despite several clinical trials.</p></div><div><h3>Objective</h3><p>To conduct a systematic review and meta-analysis of preclinical evidence regarding the effect of nitroglycerin on infarct volume in animal models of ischaemic stroke.</p></div><div><h3>Summary of review</h3><p>The protocol was registered in PROSPERO (CRD42023432644). Our search identified 238 publications. Three publications met inclusion criteria (including 10 comparisons of infarct size). Study quality was modest (median 6 out of 9), with no evidence of publication bias. Nitroglycerin did not significantly reduce infarct volume (NMD point estimate 20.2 % reduction, 95 % CI −1.52–52.7 %, <em>p</em> = 0.068). Subgroup analysis suggested greater efficacy of nitroglycerin with direct intracarotid administration to the ischaemic territory at the time of reperfusion.</p></div><div><h3>Conclusions</h3><p>A small number of studies (three) were included in this review. Overall, nitroglycerin did not reduce infarct volume in experimental stroke models. However, nitroglycerin may be of benefit when administered directly into the ischaemic territory. Given nitroglycerin's short half-life, we propose this route may minimise harmful reduction of cerebral perfusion pressure resulting from hypotension following systemic administration.</p></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1089860324001046/pdfft?md5=91e5cfa784368db27ad66c40f95a18f4&pid=1-s2.0-S1089860324001046-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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