Circulating Neurovascular Guidance Molecules and Their Relationship with Peripheral Microvascular Impairment in Systemic Sclerosis
Systemic sclerosis (SSc, scleroderma) is a complex connective tissue disease whose earliest clinical manifestations are microvascular tone dysregulation and peripheral microcirculatory abnormalities. Following previous evidence of an association between circulating neurovascular guidance molecules a...
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MDPI AG
2022-07-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/7/1056 |
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| author | Eloisa Romano Irene Rosa Bianca Saveria Fioretto Marco Matucci-Cerinic Mirko Manetti |
| author_facet | Eloisa Romano Irene Rosa Bianca Saveria Fioretto Marco Matucci-Cerinic Mirko Manetti |
| author_sort | Eloisa Romano |
| collection | DOAJ |
| description | Systemic sclerosis (SSc, scleroderma) is a complex connective tissue disease whose earliest clinical manifestations are microvascular tone dysregulation and peripheral microcirculatory abnormalities. Following previous evidence of an association between circulating neurovascular guidance molecules and SSc disturbed angiogenesis, here, we measured the levels of soluble neuropilin 1 (sNRP1), semaphorin 3E (Sema3E), and Slit2 by enzyme-linked immunosorbent assay in serum samples from a large case series of 166 SSc patients vs. 110 healthy controls. We focused on their possible correlation with vascular disease clinical features and applied logistic regression analysis to determine which of them could better reflect disease activity and severity. Our results demonstrate that, in SSc: (i) sNRP1 is significantly decreased, with lower sNRP1 serum levels correlating with the severity of nailfold videocapillaroscopy (NVC) abnormalities and the presence of ischemic digital ulcers (DUs); (ii) both Sema3E and Slit2 are increased, with Sema3E better reflecting early NVC abnormalities; and (iii) higher Sema3E correlates with the absence of DUs, while augmented Slit2 associates with the presence of DUs. Receiver operator characteristics curve analysis revealed that both circulating sNRP1 and Sema3E show a moderate diagnostic accuracy. Moreover, logistic regression analysis allowed to identify sNRP1 and Sema3E as more suitable independent biomarkers reflecting the activity and severity of SSc-related peripheral microvasculopathy. |
| first_indexed | 2024-03-09T03:16:36Z |
| format | Article |
| id | doaj.art-09de7f203fd04c588e7165ccb10e297a |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T03:16:36Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-09de7f203fd04c588e7165ccb10e297a2023-12-03T15:18:53ZengMDPI AGLife2075-17292022-07-01127105610.3390/life12071056Circulating Neurovascular Guidance Molecules and Their Relationship with Peripheral Microvascular Impairment in Systemic SclerosisEloisa Romano0Irene Rosa1Bianca Saveria Fioretto2Marco Matucci-Cerinic3Mirko Manetti4Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalySection of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDivision of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalyDivision of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalySection of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, ItalySystemic sclerosis (SSc, scleroderma) is a complex connective tissue disease whose earliest clinical manifestations are microvascular tone dysregulation and peripheral microcirculatory abnormalities. Following previous evidence of an association between circulating neurovascular guidance molecules and SSc disturbed angiogenesis, here, we measured the levels of soluble neuropilin 1 (sNRP1), semaphorin 3E (Sema3E), and Slit2 by enzyme-linked immunosorbent assay in serum samples from a large case series of 166 SSc patients vs. 110 healthy controls. We focused on their possible correlation with vascular disease clinical features and applied logistic regression analysis to determine which of them could better reflect disease activity and severity. Our results demonstrate that, in SSc: (i) sNRP1 is significantly decreased, with lower sNRP1 serum levels correlating with the severity of nailfold videocapillaroscopy (NVC) abnormalities and the presence of ischemic digital ulcers (DUs); (ii) both Sema3E and Slit2 are increased, with Sema3E better reflecting early NVC abnormalities; and (iii) higher Sema3E correlates with the absence of DUs, while augmented Slit2 associates with the presence of DUs. Receiver operator characteristics curve analysis revealed that both circulating sNRP1 and Sema3E show a moderate diagnostic accuracy. Moreover, logistic regression analysis allowed to identify sNRP1 and Sema3E as more suitable independent biomarkers reflecting the activity and severity of SSc-related peripheral microvasculopathy.https://www.mdpi.com/2075-1729/12/7/1056systemic sclerosissclerodermaneurovascular guidance moleculessNRP1Sema3ESlit2 |
| spellingShingle | Eloisa Romano Irene Rosa Bianca Saveria Fioretto Marco Matucci-Cerinic Mirko Manetti Circulating Neurovascular Guidance Molecules and Their Relationship with Peripheral Microvascular Impairment in Systemic Sclerosis Life systemic sclerosis scleroderma neurovascular guidance molecules sNRP1 Sema3E Slit2 |
| title | Circulating Neurovascular Guidance Molecules and Their Relationship with Peripheral Microvascular Impairment in Systemic Sclerosis |
| title_full | Circulating Neurovascular Guidance Molecules and Their Relationship with Peripheral Microvascular Impairment in Systemic Sclerosis |
| title_fullStr | Circulating Neurovascular Guidance Molecules and Their Relationship with Peripheral Microvascular Impairment in Systemic Sclerosis |
| title_full_unstemmed | Circulating Neurovascular Guidance Molecules and Their Relationship with Peripheral Microvascular Impairment in Systemic Sclerosis |
| title_short | Circulating Neurovascular Guidance Molecules and Their Relationship with Peripheral Microvascular Impairment in Systemic Sclerosis |
| title_sort | circulating neurovascular guidance molecules and their relationship with peripheral microvascular impairment in systemic sclerosis |
| topic | systemic sclerosis scleroderma neurovascular guidance molecules sNRP1 Sema3E Slit2 |
| url | https://www.mdpi.com/2075-1729/12/7/1056 |
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