Protective effects of angiotensin-converting enzyme I/I and matrix metalloproteinase-3 6A/6A polymorphisms on dilatative pathology within the ascending thoracic aorta

Abstract

Objective Activation of matrix metalloproteinases and the renin/angiotensin signaling pathways is under investigation with regard to their potential pathogenesis in dilatative pathology of the aorta. The purpose of this study was to explore matrix metalloproteinase-3 5A/6A and angiotensin-converting enzyme I/D polymorphisms as predisposing factors to dilatative pathology of the aorta. Methods We studied 107 patients who underwent aortic reconstruction surgery due to dilatative pathology of ascending thoracic aorta and a random sample of the population (n =773), all from Lithuania. The insertion/deletion (−1171 5A/6A) polymorphism in the promoter region of matrix metalloproteinase-3 studied by real-time polymerase-chain-reaction amplification and the D and I alleles were identified on the basis of standard polymerase-chain-reaction amplification of the respective fragments from intron 16 of the angiotensin-converting enzyme gene. Results The frequency of the angiotensin-converting enzyme D allele was significantly higher in dilatative pathology of ascending thoracic aorta patients than in the reference group subjects (0.55 vs 0.48, respectively). The latter group had a significantly higher frequency of the angiotensin-converting enzyme I/I genotype than in dilatative pathology of ascending thoracic aorta patients (27.4% vs 16.5%, respectively). In the reference group, the frequency of combined angiotensin-converting enzyme I/I and matrix metalloproteinase-3 6A/6A genotypes was 7.5%, while in the dilatative pathology of ascending thoracic aorta patient group, there was no one carrying that combined genotype (p=0.001). Conclusions The present study showing a role of angiotensin-converting enzyme and matrix metalloproteinase-3 in the development of dilatative pathology of ascending thoracic aorta permits us to entertain a possible protective mechanism for the combined effects of the angiotensin-converting enzyme I/I and the matrix metalloproteinase-3 6A/6A genotypes.

Left ventricular remodelling after acute myocardial infarction: Impact of clinical, echocardiographic parameters and polymorphism of angiotensinogen gene

“…Other effects such as increased vessel permeability, growth factor and metalloproteinases activation, haemodynamic overload through vasoconstriction and water retention, increased oxidative stress and direct cytotoxic effect leading to cell death through necrosis or apoptosis are observed. [23][24][25] Furthermore, effects of the RAS in the remodelling development can be demonstrated by effectiveness of the RAS blocking treatment on post-infarction remodelling, which was demonstrated in previous studies and trials. 8,9 In our study, we have analysed the impact of AGT polymorphism on prediction of LV remodelling.…”

Involvement of the renin–angiotensin system in abdominal and thoracic aortic aneurysms

“…Two studies have investigated the association of the I/D (insertion/deletion) polymorphism of the ACE gene with TAAs in patients with either non-Marfan's syndrome-related diseases [106] or an aortic valve abnormality [107], revealing that the D allele of the ACE gene conferred a risk of TAAs.…”

The association between copy number variant of Angiotensin Converting Enzyme gene and the risk of Ascending Aortic Aneurysm in Bicuspid and Tricuspid Aortic Valve

“…It seems that the frequency of ACE gene CNV varies widely in different surveys with various sample sizes, between abdominal versus ascending aorta, between humans and animals, and in different geographical regions [19][20][21][22][23]. a possible protective mechanism for the combined effects of these two enzymes [25].…”

“…Few researches have been conducted about occurrence of this polymorphism and ascending aortic aneurysm along with bicuspid aortic valve disease compared to tricuspid aortic valve [24][25][26][27][28].…”