Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function
(1) Background: Endothelial dysfunction initiates cardiovascular pathologies, including peripheral artery disease (PAD). The pathophysiology of impaired new vessel formation in the presence of angiogenic stimuli, such as ischemia and inflammation, is unknown. We have recently shown in mice that redu...
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MDPI AG
2023-09-01
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| Online Access: | https://www.mdpi.com/2227-9059/11/9/2459 |
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| author | Janina Krug Magdalena L. Bochenek Rajinikanth Gogiraju Dagmar Laubert-Reh Karl J. Lackner Thomas Münzel Philipp S. Wild Christine Espinola-Klein Katrin Schäfer |
| author_facet | Janina Krug Magdalena L. Bochenek Rajinikanth Gogiraju Dagmar Laubert-Reh Karl J. Lackner Thomas Münzel Philipp S. Wild Christine Espinola-Klein Katrin Schäfer |
| author_sort | Janina Krug |
| collection | DOAJ |
| description | (1) Background: Endothelial dysfunction initiates cardiovascular pathologies, including peripheral artery disease (PAD). The pathophysiology of impaired new vessel formation in the presence of angiogenic stimuli, such as ischemia and inflammation, is unknown. We have recently shown in mice that reduced endothelial protein C receptor (EPCR) expression results in defective angiogenesis following experimental hindlimb ischemia. (2) Purpose: To determine soluble (s)EPCR levels in the plasma of patients with PAD and to compare them with the protein C activity and biomarkers of endothelial function, inflammation, and angiogenesis. (3) Methods and Results: Clinical tests of vascular function and immunoassays of plasma from patients with PAD stage II were compared to age- and sex-matched individuals with and without cardiovascular risk factors or PAD stage III/IV patients. sEPCR levels were significantly lower in PAD stage II patients compared to subjects with risk factors, but no PAD, and further decreased in PAD stage III/IV patients. Plasma protein C activity or levels of ADAM17, a mediator of EPCR shedding, did not differ. Significant associations between sEPCR and the ankle-brachial index (<i>p</i> = 0.0359), age (<i>p</i> = 0.0488), body mass index (<i>p</i> = 0.0110), and plasma sE-selectin levels (<i>p</i> = 0.0327) were observed. High-sensitive CRP levels and white blood cell counts were significantly elevated in PAD patients and associated with serum glucose levels, but not sEPCR. In contrast, plasma TNFα or IL1β levels did not differ. Circulating levels of VEGF were significantly elevated in PAD stage II patients (<i>p</i> = 0.0198), but not associated with molecular (sE-selectin) or functional (ankle-brachial index) markers of vascular health. (4) Conclusions: Our findings suggest that circulating sEPCR levels may be useful as biomarkers of endothelial dysfunction, including angiogenesis, in persons older than 35 years and that progressive loss of endothelial protein C receptors might be involved in the development and progression of PAD. |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T23:00:21Z |
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| spelling | doaj.art-66be3af2eedf4c68b01816ac1303bebe2023-11-19T09:41:37ZengMDPI AGBiomedicines2227-90592023-09-01119245910.3390/biomedicines11092459Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular FunctionJanina Krug0Magdalena L. Bochenek1Rajinikanth Gogiraju2Dagmar Laubert-Reh3Karl J. Lackner4Thomas Münzel5Philipp S. Wild6Christine Espinola-Klein7Katrin Schäfer8Department of Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology III, University Medical Center Mainz, 55131 Mainz, GermanyDepartment of Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, Germany(1) Background: Endothelial dysfunction initiates cardiovascular pathologies, including peripheral artery disease (PAD). The pathophysiology of impaired new vessel formation in the presence of angiogenic stimuli, such as ischemia and inflammation, is unknown. We have recently shown in mice that reduced endothelial protein C receptor (EPCR) expression results in defective angiogenesis following experimental hindlimb ischemia. (2) Purpose: To determine soluble (s)EPCR levels in the plasma of patients with PAD and to compare them with the protein C activity and biomarkers of endothelial function, inflammation, and angiogenesis. (3) Methods and Results: Clinical tests of vascular function and immunoassays of plasma from patients with PAD stage II were compared to age- and sex-matched individuals with and without cardiovascular risk factors or PAD stage III/IV patients. sEPCR levels were significantly lower in PAD stage II patients compared to subjects with risk factors, but no PAD, and further decreased in PAD stage III/IV patients. Plasma protein C activity or levels of ADAM17, a mediator of EPCR shedding, did not differ. Significant associations between sEPCR and the ankle-brachial index (<i>p</i> = 0.0359), age (<i>p</i> = 0.0488), body mass index (<i>p</i> = 0.0110), and plasma sE-selectin levels (<i>p</i> = 0.0327) were observed. High-sensitive CRP levels and white blood cell counts were significantly elevated in PAD patients and associated with serum glucose levels, but not sEPCR. In contrast, plasma TNFα or IL1β levels did not differ. Circulating levels of VEGF were significantly elevated in PAD stage II patients (<i>p</i> = 0.0198), but not associated with molecular (sE-selectin) or functional (ankle-brachial index) markers of vascular health. (4) Conclusions: Our findings suggest that circulating sEPCR levels may be useful as biomarkers of endothelial dysfunction, including angiogenesis, in persons older than 35 years and that progressive loss of endothelial protein C receptors might be involved in the development and progression of PAD.https://www.mdpi.com/2227-9059/11/9/2459angiogenesiscoagulationendotheliumischemiaperipheral artery disease |
| spellingShingle | Janina Krug Magdalena L. Bochenek Rajinikanth Gogiraju Dagmar Laubert-Reh Karl J. Lackner Thomas Münzel Philipp S. Wild Christine Espinola-Klein Katrin Schäfer Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function Biomedicines angiogenesis coagulation endothelium ischemia peripheral artery disease |
| title | Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function |
| title_full | Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function |
| title_fullStr | Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function |
| title_full_unstemmed | Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function |
| title_short | Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function |
| title_sort | circulating soluble epcr levels are reduced in patients with ischemic peripheral artery disease and associated with markers of endothelial and vascular function |
| topic | angiogenesis coagulation endothelium ischemia peripheral artery disease |
| url | https://www.mdpi.com/2227-9059/11/9/2459 |
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