Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Jud, P.
Endothelial dysfunction in patients with limited cutaneous systemic sclerosis
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universitaet Graz; 2021. pp.99.
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- Autor*innen der Med Uni Graz:
- Jud Philipp
- Betreuer*innen:
- Brodmann Marianne
- Hafner Franz
- Meinitzer Andreas
- Altmetrics:
- Abstract:
- Background: Limited cutaneous systemic sclerosis (lcSSc) is an autoimmunological, connective tissue disorder characterized by vasculopathy, autoimmune activation and tissue fibrosis. Vasculopathy is promoted by endothelial dysfunction contributing to vascular damage including endothelial apoptosis and structural changes of the microvasculature. Only limited data are yet available for endothelial dysfunction in patients with lcSSc. The aims of this study were to investigate endothelial dysfunction, assessed by flow-mediated dilation (FMD), nitroglycerine-mediated dilation (NMD), aortic pulse-wave velocity (aPWV), endothelial microparticles (EMP), arginine, homoarginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA), and the correlations of those parameters between each other, with inflammatory parameters, as well as with clinical parameters, including vascular events and periodontal inflammation, in patients with lcSSc. Furthermore, potential differences of those parameters were also investigated within the group of patients with lcSSc between those with a disease duration of ≤ 7 years and those with a duration > 7 years. Methods: Patients with known lcSSc as well as age-, race- and sex-matched patients with primary Raynaud’s phenomenon using as controls were screened for eligibility. All patients with lcSSc and controls underwent measurements of FMD, NMD, aPWV, and biochemical analysis including inflammatory parameters, EMP, arginine, homoarginine, ADMA, and SDMA. Vascular events defined as signs of pulmonary arterial hypertension, sicca symptoms, skin, microvascular, renal, and gastrointestinal involvement were recorded by medical history including a disease-specific questionnaire, physical examination, electrocardiogram, transthoracic right heart echocardiogram, digital acral plethysmography, nailfold videocapillaroscopy, spirometry, and laboratory parameters. Additionally, dental and oral examination was performed for evaluation of periodontal inflammation. Results: After screening for eligibility, 38 patients with lcSSc with a mean age (± standard deviation [SD]) of 57.89 ± 9.22 years and a mean disease duration (± SD) of 7.11 ± 5.78 years as well as 38 age-, race- and sex-matched controls with a mean age (± SD) of 57.20 ± 8.96 years and a mean disease duration (± SD) of 5.70 ± 3.17 years were included. Neither FMD (p=0.775) nor NMD (p=0.303) nor aPWV (p=0.662) differed between patients with lcSSc and controls. In patients with lcSSc, higher values of ADMA (p=0.030) and SDMA (p=0.025) were observed, while arginine (p=0.580), homoarginine (p=0.663) and CD31+/CD42b- EMP (p=0.062) did not differ between patients with lcSSc and controls. Significant correlations were found between FMD and NMD, FMD and aPWV, ADMA and SDMA, and ADMA and CD31+/CD42b- EMP (all p<0.05). Significant differences between patients with lcSSc and controls were observed for selected skin and capillary changes, DETECT score, creatinine and estimated glomerular filtration rate (p<0.05). Between lcSSc patients with a disease duration of ≤ 7 years and lcSSc patients with a disease duration of > 7 years, only a higher rate of sclerodactyly (p=0.020) was observed in lcSSc patients with a disease duration of > 7 years, while all other parameters of endothelial dysfunction, vascular events and periodontal inflammation did not differ. Conclusion: Endothelial dysfunction affects mainly the microvascular system in patients with lcSSc while its impact on the macrovascular system remains indistinctively. Positive correlations between ADMA, SDMA and CD31+/CD42b- EMP suggest potential interaction of endothelial activation and NO metabolism in patients with lcSSc.