Synergistic Effects of Low-Frequency Ultrasound and Therapeutic Agents on Endothelial and Renal Cells: Emphasis on Cell Functionality, Oxidative Stress, and Inflammatory Markers
<b>Background:</b> Ischemic heart disease remains the leading cause of death worldwide, with coronary microvascular dysfunction (CMD) as a key complication after ST-elevation myocardial infarction (STEMI). Endothelial dysfunction contributes to CMD, impairing vascular tone and increasing...
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2025-03-01
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| author | Ieva Čiapienė Joris Vėžys Vaiva Lesauskaitė Indrė Matulevičiūtė Ugnė Meškauskaitė Vilius Skipskis Arvydas Strazdauskas Sonata Trumbeckaitė Algimantas Bubulis Vytautas Jūrėnas Vytautas Ostaševičius Vytenis Tamakauskas Vacis Tatarūnas |
| author_facet | Ieva Čiapienė Joris Vėžys Vaiva Lesauskaitė Indrė Matulevičiūtė Ugnė Meškauskaitė Vilius Skipskis Arvydas Strazdauskas Sonata Trumbeckaitė Algimantas Bubulis Vytautas Jūrėnas Vytautas Ostaševičius Vytenis Tamakauskas Vacis Tatarūnas |
| author_sort | Ieva Čiapienė |
| collection | DOAJ |
| description | <b>Background:</b> Ischemic heart disease remains the leading cause of death worldwide, with coronary microvascular dysfunction (CMD) as a key complication after ST-elevation myocardial infarction (STEMI). Endothelial dysfunction contributes to CMD, impairing vascular tone and increasing inflammation. While angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) aid vascular health, their efficacy may improve with therapeutic ultrasound, which enhances drug delivery and endothelial response. This study explores the combined effects of ultrasound and pharmacological treatment on the ACE axis and inflammation in endothelial and renal cells. <b>Methods:</b> Human umbilical vein endothelial cells (HUVECs) and human renal proximal tubular epithelial cell line RPTEC/TERT1 were treated with captopril, losartan, and dexamethasone, alone or combined with low-frequency ultrasound (LFU). Cell viability and wound-healing assays assessed cellular function, while nitric oxide (NO) and reactive oxygen species (ROS) assays were used to evaluate redox signaling. Gene expression related to the ACE axis, inflammation, and vascular and renal cell function was analyzed via qPCR. <b>Results:</b> Captopril and losartan combined with LFU improved endothelial cell viability, wound healing, and NO production at various concentrations, whereas only losartan with LFU enhanced cell viability and wound healing in renal cells. Dexamethasone with LFU increased ROS levels and had variable effects on RPTEC/TERT1 cell survival. Gene expression analysis showed that LFU alone reduced pro-inflammatory markers <i>VCAM-1</i>, <i>ICAM-1</i>, and <i>PTGS2</i> in captopril-treated HUVECs and similarly affected <i>CYP4F2</i> in losartan-treated HUVECs. LFU also decreased <i>PTGS2</i> expression at higher dexamethasone concentrations. In RPTEC/TERT1 cells, LFU alone did not impact <i>SGLT2</i> or <i>GGT1</i> expression, but captopril with LFU downregulated <i>GGT1</i>, and dexamethasone with LFU upregulated <i>SGLT2</i> at higher concentrations. <b>Conclusions:</b> This study demonstrates that LFU enhances the effects of RAS inhibitors by promoting NO synthesis and reducing oxidative stress, while its combination with dexamethasone may have variable, potentially cytotoxic effects on renal cells. Gene expression patterns suggest LFU’s anti-inflammatory potential and its role in modulating drug efficacy. |
| format | Article |
| id | doaj-art-5039d1c32372489fa60586d850db0af9 |
| institution | OA Journals |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-03-01 |
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| series | Pharmaceuticals |
| spelling | doaj-art-5039d1c32372489fa60586d850db0af92025-08-20T01:49:01ZengMDPI AGPharmaceuticals1424-82472025-03-0118340410.3390/ph18030404Synergistic Effects of Low-Frequency Ultrasound and Therapeutic Agents on Endothelial and Renal Cells: Emphasis on Cell Functionality, Oxidative Stress, and Inflammatory MarkersIeva Čiapienė0Joris Vėžys1Vaiva Lesauskaitė2Indrė Matulevičiūtė3Ugnė Meškauskaitė4Vilius Skipskis5Arvydas Strazdauskas6Sonata Trumbeckaitė7Algimantas Bubulis8Vytautas Jūrėnas9Vytautas Ostaševičius10Vytenis Tamakauskas11Vacis Tatarūnas12Institute of Cardiology, Lithuanian University of Health Sciences, Sukileliu 15, LT-50103 Kaunas, LithuaniaDepartment of Mechanical Engineering, Faculty of Mechanical Engineering and Design, Kaunas University of Technology, Studentu 56, LT-51424 Kaunas, LithuaniaInstitute of Cardiology, Lithuanian University of Health Sciences, Sukileliu 15, LT-50103 Kaunas, LithuaniaDepartment of Ophthalmology, Lithuanian University of Health Sciences, Eiveniu 2, LT-50161 Kaunas, LithuaniaInstitute of Cardiology, Lithuanian University of Health Sciences, Sukileliu 15, LT-50103 Kaunas, LithuaniaInstitute of Cardiology, Lithuanian University of Health Sciences, Sukileliu 15, LT-50103 Kaunas, LithuaniaDepartment of Biochemistry, Faculty of Medicine, Lithuanian University of Health Sciences, Eiveniu 4, LT-50161 Kaunas, LithuaniaDepartment of Pharmacognosy, Faculty of Pharmacy, Lithuanian University of Health Sciences, Sukileliu 13, LT-50162 Kaunas, LithuaniaInstitute of Mechatronics, Kaunas University of Technology, Studentu 56, LT-51424 Kaunas, LithuaniaInstitute of Mechatronics, Kaunas University of Technology, Studentu 56, LT-51424 Kaunas, LithuaniaInstitute of Mechatronics, Kaunas University of Technology, Studentu 56, LT-51424 Kaunas, LithuaniaInstitute of Cardiology, Lithuanian University of Health Sciences, Sukileliu 15, LT-50103 Kaunas, LithuaniaInstitute of Cardiology, Lithuanian University of Health Sciences, Sukileliu 15, LT-50103 Kaunas, Lithuania<b>Background:</b> Ischemic heart disease remains the leading cause of death worldwide, with coronary microvascular dysfunction (CMD) as a key complication after ST-elevation myocardial infarction (STEMI). Endothelial dysfunction contributes to CMD, impairing vascular tone and increasing inflammation. While angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) aid vascular health, their efficacy may improve with therapeutic ultrasound, which enhances drug delivery and endothelial response. This study explores the combined effects of ultrasound and pharmacological treatment on the ACE axis and inflammation in endothelial and renal cells. <b>Methods:</b> Human umbilical vein endothelial cells (HUVECs) and human renal proximal tubular epithelial cell line RPTEC/TERT1 were treated with captopril, losartan, and dexamethasone, alone or combined with low-frequency ultrasound (LFU). Cell viability and wound-healing assays assessed cellular function, while nitric oxide (NO) and reactive oxygen species (ROS) assays were used to evaluate redox signaling. Gene expression related to the ACE axis, inflammation, and vascular and renal cell function was analyzed via qPCR. <b>Results:</b> Captopril and losartan combined with LFU improved endothelial cell viability, wound healing, and NO production at various concentrations, whereas only losartan with LFU enhanced cell viability and wound healing in renal cells. Dexamethasone with LFU increased ROS levels and had variable effects on RPTEC/TERT1 cell survival. Gene expression analysis showed that LFU alone reduced pro-inflammatory markers <i>VCAM-1</i>, <i>ICAM-1</i>, and <i>PTGS2</i> in captopril-treated HUVECs and similarly affected <i>CYP4F2</i> in losartan-treated HUVECs. LFU also decreased <i>PTGS2</i> expression at higher dexamethasone concentrations. In RPTEC/TERT1 cells, LFU alone did not impact <i>SGLT2</i> or <i>GGT1</i> expression, but captopril with LFU downregulated <i>GGT1</i>, and dexamethasone with LFU upregulated <i>SGLT2</i> at higher concentrations. <b>Conclusions:</b> This study demonstrates that LFU enhances the effects of RAS inhibitors by promoting NO synthesis and reducing oxidative stress, while its combination with dexamethasone may have variable, potentially cytotoxic effects on renal cells. Gene expression patterns suggest LFU’s anti-inflammatory potential and its role in modulating drug efficacy.https://www.mdpi.com/1424-8247/18/3/404low-frequency ultrasoundRAS inhibitorscaptoprillosartandexamethasoneinflammation |
| spellingShingle | Ieva Čiapienė Joris Vėžys Vaiva Lesauskaitė Indrė Matulevičiūtė Ugnė Meškauskaitė Vilius Skipskis Arvydas Strazdauskas Sonata Trumbeckaitė Algimantas Bubulis Vytautas Jūrėnas Vytautas Ostaševičius Vytenis Tamakauskas Vacis Tatarūnas Synergistic Effects of Low-Frequency Ultrasound and Therapeutic Agents on Endothelial and Renal Cells: Emphasis on Cell Functionality, Oxidative Stress, and Inflammatory Markers Pharmaceuticals low-frequency ultrasound RAS inhibitors captopril losartan dexamethasone inflammation |
| title | Synergistic Effects of Low-Frequency Ultrasound and Therapeutic Agents on Endothelial and Renal Cells: Emphasis on Cell Functionality, Oxidative Stress, and Inflammatory Markers |
| title_full | Synergistic Effects of Low-Frequency Ultrasound and Therapeutic Agents on Endothelial and Renal Cells: Emphasis on Cell Functionality, Oxidative Stress, and Inflammatory Markers |
| title_fullStr | Synergistic Effects of Low-Frequency Ultrasound and Therapeutic Agents on Endothelial and Renal Cells: Emphasis on Cell Functionality, Oxidative Stress, and Inflammatory Markers |
| title_full_unstemmed | Synergistic Effects of Low-Frequency Ultrasound and Therapeutic Agents on Endothelial and Renal Cells: Emphasis on Cell Functionality, Oxidative Stress, and Inflammatory Markers |
| title_short | Synergistic Effects of Low-Frequency Ultrasound and Therapeutic Agents on Endothelial and Renal Cells: Emphasis on Cell Functionality, Oxidative Stress, and Inflammatory Markers |
| title_sort | synergistic effects of low frequency ultrasound and therapeutic agents on endothelial and renal cells emphasis on cell functionality oxidative stress and inflammatory markers |
| topic | low-frequency ultrasound RAS inhibitors captopril losartan dexamethasone inflammation |
| url | https://www.mdpi.com/1424-8247/18/3/404 |
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