Τίτλος:
Tissue-specific relaxin-2 is differentially associated with the presence/size of an arterial aneurysm and the severity of atherosclerotic disease in humans
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Circulating or tissue-related biomarkers are of clinical value for risk stratification in patients with abdominal aortic aneurysms. Relaxin-2 (RL2) has been linked to the presence and size of arterial aneurysms, and to the extent of atherosclerosis in human subjects. Here, we assessed the expression levels of RL2 in aneurysmal (AA, n = 16) and atherosclerotic (ATH, n = 22) arteries, and established the correlation between RL2 levels and the presence/size of AA and the clinical severity of atherosclerosis. The expression levels of metalloproteinases (MMPs) and endothelial nitric oxide synthetase (eNOS) were also detected for correlations with different phenotypes of atherosclerosis and AA. Temporal artery biopsy specimens (n = 6) and abdominal aortic tissues harvested from accident victims during autopsy (n = 10) were used as controls. Quantitative tissue biomarker analysis revealed that tissue-specific RL2 was increased in patients with larger or symptomatic AA compared to subjects with atherosclerotic disease and healthy controls. In situ RL2 levels were proportional to the size and the severity of aneurysmatic disease, and were substantially elevated in patients with symptomatic aneurysm of any diameter or asymptomatic aneurysm of a diameter >350% of that of the normal artery. In contrast, tissue RL2 was inversely associated with the clinical severity of atherosclerotic lesions. Correlation between RL2 and MMP2 was different between ATH1 and ATH2, depending on atherosclerosis grade. Overall, tissue RL2 is differentially associated with discrete phenotypes of arterial disease and might exert multipotent biological effects on vascular wall integrity and remodeling in human subjects. © 2020, CPS and SIMM.
Συγγραφείς:
Papoutsis, K.
Kapelouzou, A.
Georgiopoulos, G.
Kontogiannis, C.
Kourek, C.
Mylonas, K.S.
Patelis, N.
Cokkinos, D.V.
Karavokyros, I.
Georgopoulos, S.
Περιοδικό:
Acta Pharmacologica Sinica
Εκδότης:
Springer Nature BV
Λέξεις-κλειδιά:
endothelial nitric oxide synthase; gelatinase A; gelatinase B; serelaxin; gelatinase A; MMP2 protein, human; relaxin; RLN2 protein, human, abdominal aortic aneurysm; aged; aortic tissue; Article; atherosclerotic plaque; autopsy; blood vessel biopsy; blood vessel wall; carotid artery disease; carotid artery obstruction; carotid atherosclerosis; carotid endarterectomy; claudication; clinical article; comorbidity; controlled study; disease severity; endothelial dysfunction; female; human; human tissue; immunohistochemistry; male; mRNA expression level; open surgery; protein expression level; temporal arteritis; temporal artery; aneurysm; atherosclerosis; genetics; metabolism; severity of illness index, Aged; Aneurysm; Atherosclerosis; Female; Humans; Male; Matrix Metalloproteinase 2; Relaxin; Severity of Illness Index
DOI:
10.1038/s41401-019-0350-5
