title: Plasma endothelial microparticles reflect the extent of capillaroscopic alterations and correlate with the severity of skin involvement in systemic sclerosis.
abstract: Endothelial microparticles (EMPs) are membrane-coated vesicles shed from endothelial cells and are considered markers of the endothelial state. It has been shown that total numbers of circulating EMPs are increased in patients with systemic sclerosis (SSc), but their clinical correlations have not yet been investigated in detail. We aimed to assess possible relationships between circulating EMPs and clinical as well as laboratory features among SSc patients with special attention to possible association with alteration in microvascular morphology objectified on nailfold videocapillaroscopy and clinical signs of microvascular complications.
  
  
  
  The study included 47 SSc patients and 27 age- and sex-matched healthy controls. EMPs were identified with flow cytometry after staining platelet-poor plasma with combinations of fluorescent cell-specific monoclonal antibodies (anti-CD31, -51, -42b, -62E and Annexin V). The following types of EMPs were evaluated: total EMPs (CD31+/CD42b-), activated EMPs (CD62E+/AnnV-,) and apoptotic EMPs (CD62E+/AnnV+ or CD51+). Clinical evaluation of patients was obtained, including nailfold videocapillaroscopy.
  
  
  
  All types of EMPs were significantly elevated in SSc patients as compared with healthy controls. We found significant inverse correlation between severity of skin involvement and values of total EMPs (r=-0.32; p=0.02) and their levels tended to be lower in SSc patients with digital ulcers when compared to those without ischaemic skin lesions (p=0.09). Total EMPs and activated EMPs showed correlations with the number of ramified capillaries (r=-0.40 and r=0.37, respectively, p<0.05 for both). Moreover, total EMPs inversely correlated with the severity of capillary loss (r=-0.35, p<0.05) and their levels were significantly lower in patients with late NVC pattern with respect to those with early microangiopathy (p<0.05). On the other hand, active NVC pattern was characterized by strongly elevated levels of activated EMPs when compared to an early vascular alteration (p<0.05).
  
  
  
  Our results suggest that quantity and phenotype of circulating EMPs might indicate on molecular vascular damage with endothelial dysfunction and to reflect progressive loss of capillaries consequencing in microvascular insufficiency in SSc patients.
authors.affiliation: Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Radziwiłłowska 13, 20-080 Lublin, Poland. Electronic address: mjm@poczta.onet.eu.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Michalska-Jakubus
authors.affiliation: Department of Rheumatology and Internal Medicine, Medical University of Białystok, Skłodowskiej-Curie 24a, 15-276 Białystok, Poland. Electronic address: otylia.bielecka@gmail.com.
authors.forename: Otylia
authors.initials: O
authors.lastname: Kowal-Bielecka
authors.affiliation: Faculty of Internal Medicine, Ghent University, Belgium. Electronic address: vanessa.smith@ugent.be.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Smith
authors.affiliation: Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy. Electronic address: mcutolo@unige.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
authors.affiliation: Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Radziwiłłowska 13, 20-080 Lublin, Poland. Electronic address: dorota.krasowska@umlub.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Krasowska
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002196:Capillaries / Q000737:chemistry / Q000473:pathology*; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000737:chemistry / Q000473:pathology*; D018450:Disease Progression; D042783:Endothelial Cells / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D020678:Microscopic Angioscopy; D008875:Middle Aged; D009262:Nails / Q000098:blood supply*; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012595:Scleroderma, Systemic / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D012720:Severity of Illness Index; D012883:Skin Ulcer / Q000097:blood / Q000175:diagnosis* / Q000473:pathology
chemical_list: D015415:Biomarkers
keywords: Endothelial microparticles; Microangiopathy; Nailfold capillaroscopy; Systemic sclerosis