Lipid Profiles of Urinary Extracellular Vesicles Released during the Inactive and Active Phases of Aged Male Mice with Spontaneous Hypertension
Hypertension remains a major problem, especially in the elderly, as it increases the risk for cardiovascular, coronary artery, cerebrovascular, and kidney diseases. Extracellular vesicles (EVs) play a role in the aging process and contribute to pathophysiology. Our goal was to examine differences in...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/15397 |
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| author | Juliana Pena Lopez Mohammad-Zaman Nouri Areej Ebrahim Kevin M. Chacko Whitney C. Schramm Mohammed F. Gholam Tezcan Ozrazgat-Baslanti Nancy D. Denslow Abdel A. Alli |
| author_facet | Juliana Pena Lopez Mohammad-Zaman Nouri Areej Ebrahim Kevin M. Chacko Whitney C. Schramm Mohammed F. Gholam Tezcan Ozrazgat-Baslanti Nancy D. Denslow Abdel A. Alli |
| author_sort | Juliana Pena Lopez |
| collection | DOAJ |
| description | Hypertension remains a major problem, especially in the elderly, as it increases the risk for cardiovascular, coronary artery, cerebrovascular, and kidney diseases. Extracellular vesicles (EVs) play a role in the aging process and contribute to pathophysiology. Our goal was to examine differences in lipid profiles of urinary EVs (uEVs) collected during the inactive and active phases of aged mice and investigate whether these EVs regulate the density of lipid rafts in mouse cortical collecting duct (mpkCCD) principal cells. Here, we demonstrate the epithelial sodium channel (ENaC) inhibitor benzyl amiloride reduced systolic blood pressure in aged male mice during the inactive and active phases. Lipidomics data demonstrate differential enrichment of lipids between the two groups. For example, there are more phosphatidylethanolamine plasmalogens, particularly in the form of alkyl phosphatidylethanolamines, that are enriched in active phase uEVs compared to inactive phase uEVs from the same mice. Amiloride-sensitive transepithelial current increased more in mpkCCD cells challenged with uEVs from the active phase group. Moreover, more ENaC alpha protein was distributed to lipid raft fractions of mpkCCD cells challenged with active phase uEVs. Taken together, the identification of bioactive lipids associated with lipid rafts that are enriched in EVs released during the active phase of aged mice may offer clues to help understand lipid raft organization in recipient principal cells after EV uptake and increased renal ENaC activity, leading to a time-of-day dependent regulation of blood pressure in an aging model. |
| first_indexed | 2024-03-09T17:44:59Z |
| format | Article |
| id | doaj.art-e15dea162a014a5badaae11842512275 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:44:59Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e15dea162a014a5badaae118425122752023-11-24T11:18:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231539710.3390/ijms232315397Lipid Profiles of Urinary Extracellular Vesicles Released during the Inactive and Active Phases of Aged Male Mice with Spontaneous HypertensionJuliana Pena Lopez0Mohammad-Zaman Nouri1Areej Ebrahim2Kevin M. Chacko3Whitney C. Schramm4Mohammed F. Gholam5Tezcan Ozrazgat-Baslanti6Nancy D. Denslow7Abdel A. Alli8Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USADepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USADepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USAHypertension remains a major problem, especially in the elderly, as it increases the risk for cardiovascular, coronary artery, cerebrovascular, and kidney diseases. Extracellular vesicles (EVs) play a role in the aging process and contribute to pathophysiology. Our goal was to examine differences in lipid profiles of urinary EVs (uEVs) collected during the inactive and active phases of aged mice and investigate whether these EVs regulate the density of lipid rafts in mouse cortical collecting duct (mpkCCD) principal cells. Here, we demonstrate the epithelial sodium channel (ENaC) inhibitor benzyl amiloride reduced systolic blood pressure in aged male mice during the inactive and active phases. Lipidomics data demonstrate differential enrichment of lipids between the two groups. For example, there are more phosphatidylethanolamine plasmalogens, particularly in the form of alkyl phosphatidylethanolamines, that are enriched in active phase uEVs compared to inactive phase uEVs from the same mice. Amiloride-sensitive transepithelial current increased more in mpkCCD cells challenged with uEVs from the active phase group. Moreover, more ENaC alpha protein was distributed to lipid raft fractions of mpkCCD cells challenged with active phase uEVs. Taken together, the identification of bioactive lipids associated with lipid rafts that are enriched in EVs released during the active phase of aged mice may offer clues to help understand lipid raft organization in recipient principal cells after EV uptake and increased renal ENaC activity, leading to a time-of-day dependent regulation of blood pressure in an aging model.https://www.mdpi.com/1422-0067/23/23/15397spontaneous hypertensionENaCextracellular vesicleslipids |
| spellingShingle | Juliana Pena Lopez Mohammad-Zaman Nouri Areej Ebrahim Kevin M. Chacko Whitney C. Schramm Mohammed F. Gholam Tezcan Ozrazgat-Baslanti Nancy D. Denslow Abdel A. Alli Lipid Profiles of Urinary Extracellular Vesicles Released during the Inactive and Active Phases of Aged Male Mice with Spontaneous Hypertension International Journal of Molecular Sciences spontaneous hypertension ENaC extracellular vesicles lipids |
| title | Lipid Profiles of Urinary Extracellular Vesicles Released during the Inactive and Active Phases of Aged Male Mice with Spontaneous Hypertension |
| title_full | Lipid Profiles of Urinary Extracellular Vesicles Released during the Inactive and Active Phases of Aged Male Mice with Spontaneous Hypertension |
| title_fullStr | Lipid Profiles of Urinary Extracellular Vesicles Released during the Inactive and Active Phases of Aged Male Mice with Spontaneous Hypertension |
| title_full_unstemmed | Lipid Profiles of Urinary Extracellular Vesicles Released during the Inactive and Active Phases of Aged Male Mice with Spontaneous Hypertension |
| title_short | Lipid Profiles of Urinary Extracellular Vesicles Released during the Inactive and Active Phases of Aged Male Mice with Spontaneous Hypertension |
| title_sort | lipid profiles of urinary extracellular vesicles released during the inactive and active phases of aged male mice with spontaneous hypertension |
| topic | spontaneous hypertension ENaC extracellular vesicles lipids |
| url | https://www.mdpi.com/1422-0067/23/23/15397 |
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