tetano
Editor, Senior Moderator
FASEB J
. 2022 May;36 Suppl 1.
doi: 10.1096/fasebj.2022.36.S1.R3920.
The Role of Angiotensin 1-7 in Isolated Human Arterioles with SARS-CoV-2
Yoshinori Nishijima[SUP] 1 [/SUP], Shelby Hader[SUP] 1 [/SUP], David Zhang[SUP] 1 [/SUP], David Gutterman[SUP] 1 [/SUP], Andreas Beyer[SUP] 1 [/SUP]
Affiliations
Abstract
Introduction: The vascular endothelium plays a crucial role to regulate vascular tone. Recently, our laboratory reported severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection significantly reduced endothelial-dependent vasodilation months after exposed to SARS-CoV-2 in human microvessels. SARS-CoV-2 enters host cells through angiotensin-converting enzyme (ACE)2 as a cell surface receptor. Downregulation of ACE2 protein expression by the virus leads to imbalance between angiotensin (ANG) II and ANG 1-7, causing vasoconstriction, inflammation and increase oxidative stress. With this background, we intend to test our new hypothesis that administration of ANG 1-7 will improve vasodilation in human arterioles from previously SARS-CoV-2 positive subjects.
Methods: Fresh human tissues were obtained as de-identified surgical discarded specimens. Control subjects (n=9) were SARS-CoV-2 negative and without known virus exposure. We had 11 previously SARS-CoV-2 positive subjects or post-COVID. For all post-COVID patients, a negative COVID test was obtained prior to collection of surgical specimens. We isolated arterioles (100-200 µm) and cannulated onto glass micropipettes under 60 mmHg and examined for diameter changes to the endothelial-dependent vasodilator acetylcholine (ACh; 10[SUP]-9[/SUP] to 10[SUP]-5[/SUP] M) using videomicroscopy. Flow-mediated dilation (FMD) was recorded at steady-state during varying intraluminal pressure gradients (5-100 cm H2O). All post-COVID vessels were incubated in a culture media at 37°C for 12-15 hours with or without 1 nM of ANG 1-7.
Results: Dilation to ACh and FMD in arterioles from post-COVID was significantly reduced (ACh max. dilation at 10[SUP]-5[/SUP] M: 74±6% vs. 93±4% in control, n=7-9, P<0.001; FMD max. dilation at 100 cm H[SUB]2[/SUB] O: 49±3% vs. 86±2% in control, n=6-11, P<0.001) while overnight incubation of 1 nM ANG 1-7 significantly improved the dilation (ACh max. dilation at 10[SUP]-5[/SUP] M: 74±6% in post-COVID vs. 88±5% in post-COVID + AND 1-7, n=11, P<0.001; FMD max. dilation at 100 cm H[SUB]2[/SUB] O: 49±3% in post-COVID vs. 76±3% in post-COVID + ANG 1-7, n=11, P<0.001).
Conclusion: Administration of ANG 1-7 significantly improved vasodilation in isolated arterioles from post-COVID subjects.
. 2022 May;36 Suppl 1.
doi: 10.1096/fasebj.2022.36.S1.R3920.
The Role of Angiotensin 1-7 in Isolated Human Arterioles with SARS-CoV-2
Yoshinori Nishijima[SUP] 1 [/SUP], Shelby Hader[SUP] 1 [/SUP], David Zhang[SUP] 1 [/SUP], David Gutterman[SUP] 1 [/SUP], Andreas Beyer[SUP] 1 [/SUP]
Affiliations
- PMID: 35554320
- DOI: 10.1096/fasebj.2022.36.S1.R3920
Abstract
Introduction: The vascular endothelium plays a crucial role to regulate vascular tone. Recently, our laboratory reported severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection significantly reduced endothelial-dependent vasodilation months after exposed to SARS-CoV-2 in human microvessels. SARS-CoV-2 enters host cells through angiotensin-converting enzyme (ACE)2 as a cell surface receptor. Downregulation of ACE2 protein expression by the virus leads to imbalance between angiotensin (ANG) II and ANG 1-7, causing vasoconstriction, inflammation and increase oxidative stress. With this background, we intend to test our new hypothesis that administration of ANG 1-7 will improve vasodilation in human arterioles from previously SARS-CoV-2 positive subjects.
Methods: Fresh human tissues were obtained as de-identified surgical discarded specimens. Control subjects (n=9) were SARS-CoV-2 negative and without known virus exposure. We had 11 previously SARS-CoV-2 positive subjects or post-COVID. For all post-COVID patients, a negative COVID test was obtained prior to collection of surgical specimens. We isolated arterioles (100-200 µm) and cannulated onto glass micropipettes under 60 mmHg and examined for diameter changes to the endothelial-dependent vasodilator acetylcholine (ACh; 10[SUP]-9[/SUP] to 10[SUP]-5[/SUP] M) using videomicroscopy. Flow-mediated dilation (FMD) was recorded at steady-state during varying intraluminal pressure gradients (5-100 cm H2O). All post-COVID vessels were incubated in a culture media at 37°C for 12-15 hours with or without 1 nM of ANG 1-7.
Results: Dilation to ACh and FMD in arterioles from post-COVID was significantly reduced (ACh max. dilation at 10[SUP]-5[/SUP] M: 74±6% vs. 93±4% in control, n=7-9, P<0.001; FMD max. dilation at 100 cm H[SUB]2[/SUB] O: 49±3% vs. 86±2% in control, n=6-11, P<0.001) while overnight incubation of 1 nM ANG 1-7 significantly improved the dilation (ACh max. dilation at 10[SUP]-5[/SUP] M: 74±6% in post-COVID vs. 88±5% in post-COVID + AND 1-7, n=11, P<0.001; FMD max. dilation at 100 cm H[SUB]2[/SUB] O: 49±3% in post-COVID vs. 76±3% in post-COVID + ANG 1-7, n=11, P<0.001).
Conclusion: Administration of ANG 1-7 significantly improved vasodilation in isolated arterioles from post-COVID subjects.