Endotheliopathy in systemic sclerosis: from endothelium-dependent vasodilation to the dysfunction of the vascular reserve, is the paradise lost?

Abstract Microvascular dysfunction is considered one of the main pathogenetic pathways in systemic sclerosis (SSc), and endothelial cells plays a pivotal role even in the early phases of the disease. Endothelial dysfunction results in an early incapacity to adapt the vascular tone and the blood flow...

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Main Authors: Giulia Bandini, Silvia Bellando Randone, Mirko Manetti, Lorenzo Dagna, Marco Matucci Cerinic, Alberto Moggi Pignone
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Arthritis Research & Therapy
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Online Access:https://doi.org/10.1186/s13075-025-03568-x
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author Giulia Bandini
Silvia Bellando Randone
Mirko Manetti
Lorenzo Dagna
Marco Matucci Cerinic
Alberto Moggi Pignone
author_facet Giulia Bandini
Silvia Bellando Randone
Mirko Manetti
Lorenzo Dagna
Marco Matucci Cerinic
Alberto Moggi Pignone
author_sort Giulia Bandini
collection DOAJ
description Abstract Microvascular dysfunction is considered one of the main pathogenetic pathways in systemic sclerosis (SSc), and endothelial cells plays a pivotal role even in the early phases of the disease. Endothelial dysfunction results in an early incapacity to adapt the vascular tone and the blood flow under stress conditions, thus losing the important adaptation mechanism that is the vascular reserve. The loss of vascular tone control in systemic sclerosis is clinically evident as Raynaud’s phenomenon, one of the earliest signs of the disease. An impairment of the vascular reserve has been described in the literature for the main SSc target organs. An alteration of the coronary reserve was shown in SSc asymptomatic patients undergoing a provocative cardiac stress tests. For what concerns the pulmonary circulation, in presence of normal resting pulmonary pressure values in specific subsets of SSc patients subjected to a cycle ergometer test, an abnormal elevation of pulmonary pressure has been showed. Regarding renal arterial circulation, in SSc patients with normal baseline renal function, an absence of improved glomerular filtration after the infusion of a protein load has been demonstrated. Finally, vascular reserve can be altered even in the gastrointestinal circulation as assessed by the study of the splanchnic circulation after a balanced meal. An early detection of an alteration of the physiologic protective mechanism of the vascular reserve could open a “window of opportunity” in which SSc vasculopathy can be potentially reversible, and more responsive to targeted therapeutic strategies.
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spelling doaj-art-e16a4437d6894fcdbf0159e18fa9fac52025-08-20T01:51:36ZengBMCArthritis Research & Therapy1478-63622025-05-012711510.1186/s13075-025-03568-xEndotheliopathy in systemic sclerosis: from endothelium-dependent vasodilation to the dysfunction of the vascular reserve, is the paradise lost?Giulia Bandini0Silvia Bellando Randone1Mirko Manetti2Lorenzo Dagna3Marco Matucci Cerinic4Alberto Moggi Pignone5Department of Experimental and Clinical Medicine, Division of Internal Medicine, University of Florence, Careggi HospitalDepartment of Experimental and Clinical Medicine, Division of Rheumatology Scleroderma UNit, University of Florence, Careggi HospitalDepartment of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of FlorenceUnit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), Inflammation, Fibrosis and ageing initiative (INFLAGE), IRCCS San Raffaele Scientific Institute, and Vita-Salute San Raffaele UniversityUnit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), Inflammation, Fibrosis and ageing initiative (INFLAGE), IRCCS San Raffaele Scientific Institute, and Vita-Salute San Raffaele UniversityDepartment of Experimental and Clinical Medicine, Division of Internal Medicine, University of Florence, Careggi HospitalAbstract Microvascular dysfunction is considered one of the main pathogenetic pathways in systemic sclerosis (SSc), and endothelial cells plays a pivotal role even in the early phases of the disease. Endothelial dysfunction results in an early incapacity to adapt the vascular tone and the blood flow under stress conditions, thus losing the important adaptation mechanism that is the vascular reserve. The loss of vascular tone control in systemic sclerosis is clinically evident as Raynaud’s phenomenon, one of the earliest signs of the disease. An impairment of the vascular reserve has been described in the literature for the main SSc target organs. An alteration of the coronary reserve was shown in SSc asymptomatic patients undergoing a provocative cardiac stress tests. For what concerns the pulmonary circulation, in presence of normal resting pulmonary pressure values in specific subsets of SSc patients subjected to a cycle ergometer test, an abnormal elevation of pulmonary pressure has been showed. Regarding renal arterial circulation, in SSc patients with normal baseline renal function, an absence of improved glomerular filtration after the infusion of a protein load has been demonstrated. Finally, vascular reserve can be altered even in the gastrointestinal circulation as assessed by the study of the splanchnic circulation after a balanced meal. An early detection of an alteration of the physiologic protective mechanism of the vascular reserve could open a “window of opportunity” in which SSc vasculopathy can be potentially reversible, and more responsive to targeted therapeutic strategies.https://doi.org/10.1186/s13075-025-03568-xSystemic sclerosisVascular reserveEndotheliopathyEndothelial dysfunction
spellingShingle Giulia Bandini
Silvia Bellando Randone
Mirko Manetti
Lorenzo Dagna
Marco Matucci Cerinic
Alberto Moggi Pignone
Endotheliopathy in systemic sclerosis: from endothelium-dependent vasodilation to the dysfunction of the vascular reserve, is the paradise lost?
Arthritis Research & Therapy
Systemic sclerosis
Vascular reserve
Endotheliopathy
Endothelial dysfunction
title Endotheliopathy in systemic sclerosis: from endothelium-dependent vasodilation to the dysfunction of the vascular reserve, is the paradise lost?
title_full Endotheliopathy in systemic sclerosis: from endothelium-dependent vasodilation to the dysfunction of the vascular reserve, is the paradise lost?
title_fullStr Endotheliopathy in systemic sclerosis: from endothelium-dependent vasodilation to the dysfunction of the vascular reserve, is the paradise lost?
title_full_unstemmed Endotheliopathy in systemic sclerosis: from endothelium-dependent vasodilation to the dysfunction of the vascular reserve, is the paradise lost?
title_short Endotheliopathy in systemic sclerosis: from endothelium-dependent vasodilation to the dysfunction of the vascular reserve, is the paradise lost?
title_sort endotheliopathy in systemic sclerosis from endothelium dependent vasodilation to the dysfunction of the vascular reserve is the paradise lost
topic Systemic sclerosis
Vascular reserve
Endotheliopathy
Endothelial dysfunction
url https://doi.org/10.1186/s13075-025-03568-x
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