Associations between collagen synthesis and degradation and aortic function in arterial hypertension.
BACKGROUND
Studies have suggested that collagen accumulation in the aortic wall may contribute to the stiff aorta in arterial hypertension. However, data in human hypertension are limited. In this investigation, relations between markers of collagen metabolism and aortic function in patients with arterial hypertension were evaluated.


METHODS
We studied 72 hypertensive patients (age 53 +/- 5 years) and 27 age- and gender-matched normotensive individuals. Elastic properties of the aorta were assessed by aortic pulse wave velocity (carotid-to-femoral pulse wave velocity (PWVc-f)). Free amino-terminal propeptides of precollagen type I (PINP, reflecting collagen I synthesis), serum telopeptides of collagen type I (CITP, an index of collagen I degradation), free amino-terminal propeptides on precollagen type III (PIIINP, reflecting collagen III metabolism), prometalloproteinase-1 (proMMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were determined by commercially available immunoassays.


RESULTS
Patients with arterial hypertension had greater PWVc-f (P = 0.01); and higher levels of PINP/CITP compared to control (P = 0.04). PWVc-f was significantly associated with PINP/CITP ratio (analysis of variance (ANOVA), P = 0.03). Hypertensive patients had significantly higher levels of proMMP-1/TIMP-1 (P = 0.04); PWVc-f was significantly associated with proMMP-1 (ANOVA, P = 0.03) and proMMP-1/TIMP-1 (ANOVA, P = 0.04). Associations between PWVc-f and proMMP-1 and between PWVc-f and PINP/CITP ratio remained significant after adjustment for PWVc-f confounders and antihypertensive treatment.


CONCLUSIONS
Alterations in collagen turnover that favor collagen type I synthesis; as well as proMMP-1 expression are related to increased aortic stiffness in treated hypertensive individuals without left ventricular (LV) hypertrophy.
Stakos
Dimitrios A
DA
Department of Cardiology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. dstakos@med.duth.gr
Tziakas
Dimitrios N
DN
Chalikias
George K
GK
Mitrousi
Kostantina
K
Tsigalou
Christina
C
Boudoulas
Harisios
H
D001011:Aorta / Q000503:physiopathology*; D016022:Case-Control Studies; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D004548:Elasticity / Q000502:physiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D024042:Collagen Type I; D010446:Peptide Fragments; D011347:Procollagen; D019715:Tissue Inhibitor of Metalloproteinase-1; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide; D003094:Collagen; D020781:Matrix Metalloproteinase 1