Dilatation of the ascending aorta and serum alpha 1-antitrypsin level in patients with bicuspid aortic valve

Abstract

Predictors of aortic dilatation are not well described in patients with bicuspid aortic valves (BAV). This study sought to examine the relationship between proximal aortic dilatation and matrix metalloproteinase-9 (MMP-9) and alpha 1-antitrypsin (α1AT) levels in patients with BAV. All patients underwent echocardiography using a standard protocol, and aortic measurements were taken in end-diastole. We studied 82 patients with BAV and categorized them into two groups according to aortic dimensions corrected for body surface area and age. The plasma level of α1AT was routinely determined using a BN ProSpec analyzer (Siemens Healthcare Diagnostics, Marburg, Germany), and that of MMP-9 were determined by ELISA (RayBiotech Inc. Norcross, GA, USA). Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS; SPSS Inc., Chicago, IL, USA) software for Windows version 12. This study included patients with BAV with no or mild valvular impairment. There were no significant differences between groups in terms of gender, body surface area, associated hypertension, diabetes mellitus, hyperlipidemia, or smoking. The mean ascending aortic diameter was 4.38 ± 0.5 mm in group 1 and 3.34 ± 0.35 mm in group 2 (p < 0.001). Plasma concentration of α1AT in patients with ascending aortic dilatation was significantly lower than that in the non-dilated group (1.32 ± 0.27 and 1.49 ± 0.25 g/l, respectively; p = 0.005). However, no significant difference was found in the MMP-9 level between the two groups (336.49 ± 233.11 and 336.39 ± 268.072 pg/ml, respectively; p = 0.96). We observed a significantly negative correlation between ascending aortic diameter and α1AT level (r = -0.300, p = 0.006) and a positive correlation between ascending aortic diameter and age (r = 0.413, p < 0.001). No significant correlation was found between plasma MMP-9 concentration and ascending aortic diameter (r = -0.008, p = 0.94). A multiple linear regression analysis was performed, including age, α1AT level, MMP-9 level, and left ventricular diastolic diameter. In this analysis, α1AT level and age were the independent predictors of aortic dilatation (p = 0.03 and p = 0.02, respectively).

Circulating matrix metalloproteinase patterns in association with aortic dilatation in bicuspid aortic valve patients with isolated severe aortic stenosis

“…On the contrary, Ikonomidis et al [28] advocated the predictive value of plasma MMP-9 for identifying ascending aortic aneurysm among BAV patients, regardless of their aortic valve status. We hypothesized that there might be different aortic vessel wall shear stress thresholds for the activation of these two enzymatic proteins, since MMP-2 was synthesized by resident cells within aortic wall such as fibroblasts and smooth muscle cells and expressed ubiquitously under physiological conditions, while MMP-9 existed mainly not only in neutrophils but also in other cell types responding to specific stimuli [29][30][31][32]. The up-regulated MMP-9 could induce endothelial dysfunction and further accelerate ascending aortic dilatation in BAV patients with severe stenosis via activation of endothelial MMP-2 [33,34].…”

Ascending Aortic Wall Cohesion: Comparison of Bicuspid and Tricuspid Valves

“…A recently published study showed that in patients presenting with bicuspid AV, plasma concentrations of α 1AT were higher in those patients with ascending aortic dilatation compared to the nondilated group [9]. Patients with bicuspid AV and a rapid progression of aortic dilatation have a more extensive cardiovascular risk profile including higher blood glucose levels, a higher incidence of coronary artery disease, more tobacco use, and a higher National Heart, Lung and Blood Institute 10-year risk of developing coronary heart disease.…”

Understanding and treating aortopathy in bicuspid aortic valve

“…MMP isoform 9 expression in aneurysmal BAV aortic tissue has been shown [14,40]. Yet several other investigations did not find meaningful differences in the plasma expression, mRNA, or allelic makeup of MMP in affected individuals [41][42][43][44].…”