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.

Oxidised low-density lipoprotein and arterial function in beta-thalassemia major.

OBJECTIVES: Vascular abnormalities such as endothelial dysfunction and arterial stiffness have been described in patients with beta-thalassemia major (beta-TM). Increased concentrations of oxidised low-density lipoprotein cholesterol (oxLDL) have been observed in those patients, but possible associations between oxLDL and arterial function in beta-TM have not been defined. METHODS: Twenty-six patients (11 males) with beta-TM (age 23 +/- 4 yr) and 30 age and gender-matched healthy subjects were studied. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWVc-f) using applanation tonometry; brachio-radial artery stiffness was assessed by carotid-radial PWV (PWVc-r). Flow-mediated dilatation (FMD) of the brachial artery and oxLDL (ELISA) were also measured. RESULTS: Patients with beta-TM had higher oxLDL levels (68.6 +/- 13.7 mU/mg vs. 50.0 +/- 12.6 mU/mg, P = 0.005), decreased FMD (3.6 +/- 2.5% vs. 7.3 +/- 3.5%, P = 0.001) and higher PWVc-f compared with controls (8.4 +/- 1.7 vs. 7.2 +/- 1.1. P < 0.002). FMD of the brachial artery was negatively associated with OxLDL concentrations in simple linear (r(2) = -0.25, P = 0.001) and multiple linear regression analysis (beta = -0.242, P = 0.03, R(2) = 0.43, P = 0.0002). PWVc-r was positively associated with OxLDL (r(2) = 0.23, P = 0.003) and showed a tendency in multiple regression analysis (beta = 0.18, P = 0.05). PWVc-r and FMD were also significantly correlated (beta = -0.213, P = 0.04) in beta-TM patients. There was no association between oxLDL and PWVc-f. CONCLUSION: An association between oxLDL, arterial elastic properties and endothelial dysfunction of muscular arteries was found. OxLDL may represent a contributing factor for the vascular manifestations described in beta-TM patients.