TY - JOUR
T1 - Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis
T2 - Findings with the soluble adhesion molecules e-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1
AU - Andersen, Grethe Neumann
AU - Caidahl, Kenneth
AU - Kazzam, Elsadig
AU - Petersson, Ann Sofi
AU - Waldenström, Anders
AU - Mincheva-Nilsson, Lucia
AU - Rantapää-Dahlqvist, Solbritt
PY - 2000/5
Y1 - 2000/5
N2 - Objective. To determine the relationship between vascular function and the inflammatory response in systemic sclerosis (SSc), and to investigate whether production of endothelial-derived nitric oxide (NO) is disturbed in this disease. Methods. We measured plasma nitrate, urinary excretion of both nitrate and cGMP, and soluble adhesion molecules of endothelial origin in patients with SSc and in age- and sex-matched controls and compared these levels between groups. Additionally, we performed correlation analysis to determine how these variables were related to one another. Plasma nitrate and 24-hour-urinary excretion of nitrate in patients and controls were measured after a 72-hour nitrate-free-diet, using a gas chromatography/mass spectrometric method. Soluble adhesion molecules intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and E- selectin and cytokines were measured by enzyme-linked immunosorbent assay. The expression of E-selectin was further investigated in skin biopsy specimens by immunoperoxidase staining, and the presence of inducible NO synthase by immunoblotting. Results. Plasma nitrate and 24-hour-urinary- excretion of cGMP were significantly elevated in patients compared with controls, while 24-hour-urinary-excretion of nitrate tended to be elevated in SSc patients. Levels of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in the patients. Levels of plasma nitrate in the patients correlated significantly with levels of sVCAM-1 (P = 0.020) and sE-selectin (P = 0.018) and approached a significant correlation with sICAM-1 (P = 0.055), suggesting that activated endothelial cells may produce plasma nitrate. Conclusion. NO synthesis is elevated in SSc patients, and the activated endothelial cell is a likely site of its production.
AB - Objective. To determine the relationship between vascular function and the inflammatory response in systemic sclerosis (SSc), and to investigate whether production of endothelial-derived nitric oxide (NO) is disturbed in this disease. Methods. We measured plasma nitrate, urinary excretion of both nitrate and cGMP, and soluble adhesion molecules of endothelial origin in patients with SSc and in age- and sex-matched controls and compared these levels between groups. Additionally, we performed correlation analysis to determine how these variables were related to one another. Plasma nitrate and 24-hour-urinary excretion of nitrate in patients and controls were measured after a 72-hour nitrate-free-diet, using a gas chromatography/mass spectrometric method. Soluble adhesion molecules intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and E- selectin and cytokines were measured by enzyme-linked immunosorbent assay. The expression of E-selectin was further investigated in skin biopsy specimens by immunoperoxidase staining, and the presence of inducible NO synthase by immunoblotting. Results. Plasma nitrate and 24-hour-urinary- excretion of cGMP were significantly elevated in patients compared with controls, while 24-hour-urinary-excretion of nitrate tended to be elevated in SSc patients. Levels of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in the patients. Levels of plasma nitrate in the patients correlated significantly with levels of sVCAM-1 (P = 0.020) and sE-selectin (P = 0.018) and approached a significant correlation with sICAM-1 (P = 0.055), suggesting that activated endothelial cells may produce plasma nitrate. Conclusion. NO synthesis is elevated in SSc patients, and the activated endothelial cell is a likely site of its production.
UR - http://www.scopus.com/inward/record.url?scp=0034049907&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034049907&partnerID=8YFLogxK
U2 - 10.1002/1529-0131(200005)43:5<1085::AID-ANR19>3.0.CO;2-7
DO - 10.1002/1529-0131(200005)43:5<1085::AID-ANR19>3.0.CO;2-7
M3 - Article
C2 - 10817563
AN - SCOPUS:0034049907
SN - 2326-5191
VL - 43
SP - 1085
EP - 1093
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 5
ER -