Patients with AS and SLE may develop cardiovascular manifestations ranging from asymptomatic forms to life threatening conditions, including common cardiovascular manifestation and valvular problems [2, 3]. The mechanism responsible for the occurrence and progression of aortic dilatation has also not yet been elucidated in detail. Aortic aneurysm may be the result of the medial degeneration, induced by chronic inflammation and accelerated by prolonged corticosteroid therapy.
Aneurism formation may be more common in patients with the coexistence of BAV. In fact, bicuspid aortic valve is considered to be a cause of intrinsic changes in the aortic wall resulting in aneurysms of the ascending aorta, independent of degree of valvular dysfunction .
In addition to the presence of BAV and the inflammatory involvement of the aortic wall by immune diseases and systemic hypertension, genetic factors may contribute significantly to the development of aortic dilation in our patient. Indeed, our observations are in agreement with such hypothesis, reporting the presence of homozygosity for genetic variants of MMP9, ACE, MTHFR and PAI-1 genes that have been previously associated with a significant risk of abdominal aortic aneurysm disease . Expression of MMP-9 is elevated in vascular disease, and in particular within aneurysm tissues. A meta-analysis of 2 larger case-control studies that have looked at the ACE I/D polymorphism in AAA patients showed a strong overall association between ACE D allele (RR 1.33 [1.20e1.48]) and disease .
An association between the presence of AAA and elevated MTHFR 677C>T has been indicated, and meta-analysis of these studies reveal a significant increased risk of AAA disease for the T allele variant . Recently, a study suggested a significant association between growth and plasminogen activator inhibitor (PAI) 1–675 4G/5G and AAA .
In the present case report, in addition to inflammatory involvement of the aortic wall by systemic autoimmune diseases, these specific genetic variants may have promoted the development of aortic dilation in this patient.
BAV is responsible for a large proportion of patients coming to aortic valve replacement. The mechanism responsible for the associated vascular complications remains controversial. Some patients with BAV have rapidly progressive valve and aortic dysfunction while some remain without complications.
Several advances in the molecular genetics of aortic valve disease related to BAV, have recently been made, especially through the use of linkage analysis. These resulted in the discovery of mutations in NOTCH1 gene, a signaling and transcriptional regulator gene on chromosome 9, NOTCH1 and some different loci linked to BAV on chromosomes 18, 5, and 13 .
However, genetic basis of BAV remains unclear. Our data suggest, for the first time, that some genetic biomarkers (functional polymorphisms) may predispose BAV patients at an increased risk of aortic dilatation, aneurysm formation, and dissection. Our findings are hypothesis generating and need to be confirmed by further clinical studies.
Elucidating the genetic basis for BAV may have substantial implications in clinical practice. Identification of specific genetic markers may helpful for early clinical detection of relatives; genetic markers might be also used to predict the natural progression of the condition and to identify those cases that might have potentially life-threatening complications from BAV
Therefore, future studies focusing on the identification of additional disease-causing and susceptibility genes are needed in order to improve understanding of the pathophysiological processes as well as to identify new therapeutic strategies.