Role of extracellular matrix proteins, matrix metalloproteinase activity and arterial stiffness in ascending aorta dilatation

Abstract

Objectives: The purpose of this study was to evaluate potential mechanisms promoting ascending aorta aneurysm (AAA) development in the pts with different pathology. Design and methods: Aortic tissue samples were collected during operation from 50 pts with AAA: 16 pts with atherosclerosis (AS) (mean age 60.1±1.6 yrs; 1.5:1, ratio m:f), 22 pts with bicuspid aortic valves (BAV) (mean age 55.7±1.9 yrs; 1.6:1, ratio m:f) and 12 pts with tricuspid valves (TAV) (mean age 50.4±4.3 yrs; 1.7:1, ratio m:f). Tissue samples were collected from 17 pts without aortic pathology (mean age 56.5±3.5 yrs). Matrix metalloproteinase (MMP) -2,-9 activities were assessed in aortic tissue homogenates by substrate-specific zymographic analysis. The relative abundances of latent MMP-2,9, collagen I, elastin and fibrillin were determined by quantitative immunoblotting techniques. Arterial stiffness was assessed by SphygmoCor device (Australia) using indirect carotid-femoral distance. The normal value of pulse wave velocity (PWV) was considered below 10 m/s. Results: There were no significant differences in thoracic aorta diameter between the groups (65.4±13.3 mm in AS, vs 58.0±4.8 mm in BAV vs 64.1±12.9 mm in TAV). Latent MMP2 was increased in all AAA groups compared with controls (BAV, TAV and AS p=0.003, p=0.029, p=0.007, respectively). But latent MMP9 was higher only in BAV group (p=0.04). Aortic dilatation in pts with BAV was associated with increased active MMP-9 level (r=0.66, p=0.037). There was increased the collagen/elastin ratio in all pts with AAA, but significant only in BAV (3.2±2.3) compared with controls (1.1±0.5, p=0.018). An increase of collagen content was correlated with active MMP9 level in pts with AS (r=0.559, p=0.037), whereas change of collagen/elastin ratio in pts with BAV was associated with increased latent MMP2 (r=0.608, p=0.02). Tendency to increase of latent and active MMP9 level was related with increase of index augmentation in all groups. Conclusions: Composition of the extracellular matrix determines the MMP activity and plays an important role in the pathogenesis of AAA. More significant changes in the composition of the extracellular matrix proteins may explain the rapid increase in the aorta diameter in pts with BAV. Arterial stiffness can be used as a marker for noninvasive monitoring of patients with aortic dilatation.