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Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles
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| Zeitschriftentitel: | Journal of the American Heart Association |
|---|---|
| Personen und Körperschaften: | , , , , , , , , |
| In: | Journal of the American Heart Association, 8, 2019, 11 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Ovid Technologies (Wolters Kluwer Health)
|
| Schlagwörter: |
| author_facet |
Santelli, Adrian Sun, In O. Eirin, Alfonso Abumoawad, Abdelrhman M. Woollard, John R. Lerman, Amir Textor, Stephen C. Puranik, Amrutesh S. Lerman, Lilach O. Santelli, Adrian Sun, In O. Eirin, Alfonso Abumoawad, Abdelrhman M. Woollard, John R. Lerman, Amir Textor, Stephen C. Puranik, Amrutesh S. Lerman, Lilach O. |
|---|---|
| author |
Santelli, Adrian Sun, In O. Eirin, Alfonso Abumoawad, Abdelrhman M. Woollard, John R. Lerman, Amir Textor, Stephen C. Puranik, Amrutesh S. Lerman, Lilach O. |
| spellingShingle |
Santelli, Adrian Sun, In O. Eirin, Alfonso Abumoawad, Abdelrhman M. Woollard, John R. Lerman, Amir Textor, Stephen C. Puranik, Amrutesh S. Lerman, Lilach O. Journal of the American Heart Association Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles Cardiology and Cardiovascular Medicine |
| author_sort |
santelli, adrian |
| spelling |
Santelli, Adrian Sun, In O. Eirin, Alfonso Abumoawad, Abdelrhman M. Woollard, John R. Lerman, Amir Textor, Stephen C. Puranik, Amrutesh S. Lerman, Lilach O. 2047-9980 Ovid Technologies (Wolters Kluwer Health) Cardiology and Cardiovascular Medicine http://dx.doi.org/10.1161/jaha.119.012584 <jats:sec xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en"> Hypertension may be associated with renal cellular injury. Cells in distress release extracellular vesicles ( <jats:styled-content style="fixed-case">EV</jats:styled-content> s), and their numbers in urine may reflect renal injury. Cellular senescence, an irreversible growth arrest in response to a noxious milieu, is characterized by release of proinflammatory cytokines. We hypothesized that <jats:styled-content style="fixed-case">EV</jats:styled-content> s released by senescent nephron cells can be identified in urine of patients with hypertension. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> We recruited patients with essential hypertension ( <jats:styled-content style="fixed-case">EH</jats:styled-content> ) or renovascular hypertension and healthy volunteers (n=14 each). Renal oxygenation was assessed using magnetic resonance imaging and blood samples collected from both renal veins for cytokine‐level measurements. <jats:styled-content style="fixed-case">EV</jats:styled-content> s isolated from urine samples were characterized by imaging flow cytometry based on specific markers, including p16 (senescence marker), calyxin (podocytes), urate transporter 1 (proximal tubules), uromodulin (ascending limb of Henle's loop), and prominin‐2 (distal tubules). Overall percentage of urinary p16+ <jats:styled-content style="fixed-case">EV</jats:styled-content> s was elevated in <jats:styled-content style="fixed-case">EH</jats:styled-content> and renovascular hypertension patients compared with healthy volunteers and correlated inversely with renal function and directly with renal vein cytokine levels. Urinary levels of p16 <jats:sup>+</jats:sup> /urate transporter 1 <jats:sup>+</jats:sup> were elevated in all hypertensive subjects compared with healthy volunteers, whereas p16 <jats:sup>+</jats:sup> /prominin‐2 <jats:sup>+</jats:sup> levels were elevated only in <jats:styled-content style="fixed-case">EH</jats:styled-content> versus healthy volunteers and p16 <jats:sup>+</jats:sup> /uromodulin <jats:sup>+</jats:sup> in renovascular hypertension versus <jats:styled-content style="fixed-case">EH</jats:styled-content> . </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en"> Levels of p16 <jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">EV</jats:styled-content> s are elevated in urine of hypertensive patients and may reflect increased proximal tubular cellular senescence. In <jats:styled-content style="fixed-case">EH</jats:styled-content> , <jats:styled-content style="fixed-case">EV</jats:styled-content> s originate also from distal tubules and in renovascular hypertension from Henle's loop. Hence, urinary <jats:styled-content style="fixed-case">EV</jats:styled-content> s levels may be useful to identify intrarenal sites of cellular senescence. </jats:p> </jats:sec> Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles Journal of the American Heart Association |
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10.1161/jaha.119.012584 |
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Online Free |
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Medizin |
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DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 |
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Ovid Technologies (Wolters Kluwer Health), 2019 |
| imprint_str_mv |
Ovid Technologies (Wolters Kluwer Health), 2019 |
| issn |
2047-9980 |
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2047-9980 |
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santelli2019senescentkidneycellsinhypertensivepatientsreleaseurinaryextracellularvesicles |
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2019 |
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Ovid Technologies (Wolters Kluwer Health) |
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ai |
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ai |
| series |
Journal of the American Heart Association |
| source_id |
49 |
| title |
Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles |
| title_unstemmed |
Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles |
| title_full |
Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles |
| title_fullStr |
Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles |
| title_full_unstemmed |
Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles |
| title_short |
Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles |
| title_sort |
senescent kidney cells in hypertensive patients release urinary extracellular vesicles |
| topic |
Cardiology and Cardiovascular Medicine |
| url |
http://dx.doi.org/10.1161/jaha.119.012584 |
| publishDate |
2019 |
| physical |
|
| description |
<jats:sec xml:lang="en">
<jats:title>Background</jats:title>
<jats:p xml:lang="en">
Hypertension may be associated with renal cellular injury. Cells in distress release extracellular vesicles (
<jats:styled-content style="fixed-case">EV</jats:styled-content>
s), and their numbers in urine may reflect renal injury. Cellular senescence, an irreversible growth arrest in response to a noxious milieu, is characterized by release of proinflammatory cytokines. We hypothesized that
<jats:styled-content style="fixed-case">EV</jats:styled-content>
s released by senescent nephron cells can be identified in urine of patients with hypertension.
</jats:p>
</jats:sec>
<jats:sec xml:lang="en">
<jats:title>Methods and Results</jats:title>
<jats:p xml:lang="en">
We recruited patients with essential hypertension (
<jats:styled-content style="fixed-case">EH</jats:styled-content>
) or renovascular hypertension and healthy volunteers (n=14 each). Renal oxygenation was assessed using magnetic resonance imaging and blood samples collected from both renal veins for cytokine‐level measurements.
<jats:styled-content style="fixed-case">EV</jats:styled-content>
s isolated from urine samples were characterized by imaging flow cytometry based on specific markers, including p16 (senescence marker), calyxin (podocytes), urate transporter 1 (proximal tubules), uromodulin (ascending limb of Henle's loop), and prominin‐2 (distal tubules). Overall percentage of urinary p16+
<jats:styled-content style="fixed-case">EV</jats:styled-content>
s was elevated in
<jats:styled-content style="fixed-case">EH</jats:styled-content>
and renovascular hypertension patients compared with healthy volunteers and correlated inversely with renal function and directly with renal vein cytokine levels. Urinary levels of p16
<jats:sup>+</jats:sup>
/urate transporter 1
<jats:sup>+</jats:sup>
were elevated in all hypertensive subjects compared with healthy volunteers, whereas p16
<jats:sup>+</jats:sup>
/prominin‐2
<jats:sup>+</jats:sup>
levels were elevated only in
<jats:styled-content style="fixed-case">EH</jats:styled-content>
versus healthy volunteers and p16
<jats:sup>+</jats:sup>
/uromodulin
<jats:sup>+</jats:sup>
in renovascular hypertension versus
<jats:styled-content style="fixed-case">EH</jats:styled-content>
.
</jats:p>
</jats:sec>
<jats:sec xml:lang="en">
<jats:title>Conclusions</jats:title>
<jats:p xml:lang="en">
Levels of p16
<jats:sup>+</jats:sup>
<jats:styled-content style="fixed-case">EV</jats:styled-content>
s are elevated in urine of hypertensive patients and may reflect increased proximal tubular cellular senescence. In
<jats:styled-content style="fixed-case">EH</jats:styled-content>
,
<jats:styled-content style="fixed-case">EV</jats:styled-content>
s originate also from distal tubules and in renovascular hypertension from Henle's loop. Hence, urinary
<jats:styled-content style="fixed-case">EV</jats:styled-content>
s levels may be useful to identify intrarenal sites of cellular senescence.
</jats:p>
</jats:sec> |
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| author | Santelli, Adrian, Sun, In O., Eirin, Alfonso, Abumoawad, Abdelrhman M., Woollard, John R., Lerman, Amir, Textor, Stephen C., Puranik, Amrutesh S., Lerman, Lilach O. |
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| description | <jats:sec xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en"> Hypertension may be associated with renal cellular injury. Cells in distress release extracellular vesicles ( <jats:styled-content style="fixed-case">EV</jats:styled-content> s), and their numbers in urine may reflect renal injury. Cellular senescence, an irreversible growth arrest in response to a noxious milieu, is characterized by release of proinflammatory cytokines. We hypothesized that <jats:styled-content style="fixed-case">EV</jats:styled-content> s released by senescent nephron cells can be identified in urine of patients with hypertension. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> We recruited patients with essential hypertension ( <jats:styled-content style="fixed-case">EH</jats:styled-content> ) or renovascular hypertension and healthy volunteers (n=14 each). Renal oxygenation was assessed using magnetic resonance imaging and blood samples collected from both renal veins for cytokine‐level measurements. <jats:styled-content style="fixed-case">EV</jats:styled-content> s isolated from urine samples were characterized by imaging flow cytometry based on specific markers, including p16 (senescence marker), calyxin (podocytes), urate transporter 1 (proximal tubules), uromodulin (ascending limb of Henle's loop), and prominin‐2 (distal tubules). Overall percentage of urinary p16+ <jats:styled-content style="fixed-case">EV</jats:styled-content> s was elevated in <jats:styled-content style="fixed-case">EH</jats:styled-content> and renovascular hypertension patients compared with healthy volunteers and correlated inversely with renal function and directly with renal vein cytokine levels. Urinary levels of p16 <jats:sup>+</jats:sup> /urate transporter 1 <jats:sup>+</jats:sup> were elevated in all hypertensive subjects compared with healthy volunteers, whereas p16 <jats:sup>+</jats:sup> /prominin‐2 <jats:sup>+</jats:sup> levels were elevated only in <jats:styled-content style="fixed-case">EH</jats:styled-content> versus healthy volunteers and p16 <jats:sup>+</jats:sup> /uromodulin <jats:sup>+</jats:sup> in renovascular hypertension versus <jats:styled-content style="fixed-case">EH</jats:styled-content> . </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en"> Levels of p16 <jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">EV</jats:styled-content> s are elevated in urine of hypertensive patients and may reflect increased proximal tubular cellular senescence. In <jats:styled-content style="fixed-case">EH</jats:styled-content> , <jats:styled-content style="fixed-case">EV</jats:styled-content> s originate also from distal tubules and in renovascular hypertension from Henle's loop. Hence, urinary <jats:styled-content style="fixed-case">EV</jats:styled-content> s levels may be useful to identify intrarenal sites of cellular senescence. </jats:p> </jats:sec> |
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| series | Journal of the American Heart Association |
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| spelling | Santelli, Adrian Sun, In O. Eirin, Alfonso Abumoawad, Abdelrhman M. Woollard, John R. Lerman, Amir Textor, Stephen C. Puranik, Amrutesh S. Lerman, Lilach O. 2047-9980 Ovid Technologies (Wolters Kluwer Health) Cardiology and Cardiovascular Medicine http://dx.doi.org/10.1161/jaha.119.012584 <jats:sec xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en"> Hypertension may be associated with renal cellular injury. Cells in distress release extracellular vesicles ( <jats:styled-content style="fixed-case">EV</jats:styled-content> s), and their numbers in urine may reflect renal injury. Cellular senescence, an irreversible growth arrest in response to a noxious milieu, is characterized by release of proinflammatory cytokines. We hypothesized that <jats:styled-content style="fixed-case">EV</jats:styled-content> s released by senescent nephron cells can be identified in urine of patients with hypertension. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> We recruited patients with essential hypertension ( <jats:styled-content style="fixed-case">EH</jats:styled-content> ) or renovascular hypertension and healthy volunteers (n=14 each). Renal oxygenation was assessed using magnetic resonance imaging and blood samples collected from both renal veins for cytokine‐level measurements. <jats:styled-content style="fixed-case">EV</jats:styled-content> s isolated from urine samples were characterized by imaging flow cytometry based on specific markers, including p16 (senescence marker), calyxin (podocytes), urate transporter 1 (proximal tubules), uromodulin (ascending limb of Henle's loop), and prominin‐2 (distal tubules). Overall percentage of urinary p16+ <jats:styled-content style="fixed-case">EV</jats:styled-content> s was elevated in <jats:styled-content style="fixed-case">EH</jats:styled-content> and renovascular hypertension patients compared with healthy volunteers and correlated inversely with renal function and directly with renal vein cytokine levels. Urinary levels of p16 <jats:sup>+</jats:sup> /urate transporter 1 <jats:sup>+</jats:sup> were elevated in all hypertensive subjects compared with healthy volunteers, whereas p16 <jats:sup>+</jats:sup> /prominin‐2 <jats:sup>+</jats:sup> levels were elevated only in <jats:styled-content style="fixed-case">EH</jats:styled-content> versus healthy volunteers and p16 <jats:sup>+</jats:sup> /uromodulin <jats:sup>+</jats:sup> in renovascular hypertension versus <jats:styled-content style="fixed-case">EH</jats:styled-content> . </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en"> Levels of p16 <jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">EV</jats:styled-content> s are elevated in urine of hypertensive patients and may reflect increased proximal tubular cellular senescence. In <jats:styled-content style="fixed-case">EH</jats:styled-content> , <jats:styled-content style="fixed-case">EV</jats:styled-content> s originate also from distal tubules and in renovascular hypertension from Henle's loop. Hence, urinary <jats:styled-content style="fixed-case">EV</jats:styled-content> s levels may be useful to identify intrarenal sites of cellular senescence. </jats:p> </jats:sec> Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles Journal of the American Heart Association |
| spellingShingle | Santelli, Adrian, Sun, In O., Eirin, Alfonso, Abumoawad, Abdelrhman M., Woollard, John R., Lerman, Amir, Textor, Stephen C., Puranik, Amrutesh S., Lerman, Lilach O., Journal of the American Heart Association, Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles, Cardiology and Cardiovascular Medicine |
| title | Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles |
| title_full | Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles |
| title_fullStr | Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles |
| title_full_unstemmed | Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles |
| title_short | Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles |
| title_sort | senescent kidney cells in hypertensive patients release urinary extracellular vesicles |
| title_unstemmed | Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles |
| topic | Cardiology and Cardiovascular Medicine |
| url | http://dx.doi.org/10.1161/jaha.119.012584 |