If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Royal Children's Hospital, Melbourne, AustraliaMurdoch Children's Research Institute, Melbourne, AustraliaUniversity of Melbourne, Melbourne, AustraliaMelbourne Children's Centre for Cardiovascular Genomics and Regenerative Medicine, Melbourne, Australia
An explosive development of global molecular assessment technology during the recent decades has resulted in the multitude of “-omic” approaches awaiting to be translated into surgical practice. To most surgeons, however, genomics, proteomics, metabolomics, comics, and other “-omics” are of very similar predictive and entertaining value. Namely, often the “-omics” do not predict anything and are somewhat mildly entertaining, at least as far as the surgical outcomes are concerned. This is the current state of affair in surgical “-omics”. But for how long? With the rapid refinement of the “-omic” technology, one cannot help wondering what surgical “-omics” may come, and what diagnostic value will come of it.
A novel and fascinating proteomic study reported in this issue of the Journal has been performed by Chiriani and colleagues
in attempt to shed light on the causes of the late autograft failure after the Ross operation. It is indeed unclear why some patients develop autograft failure develop while others do not, even after seemingly identical Ross operations.
Extensive imaging and histologic studies have been performed to determine whether the increase in size of the autograft is due to actual growth of the implanted tissue or rather is merely attributable to tissue stretching.
have provided a valuable contribution to the general understanding of this process at the proteomic level. They investigated the changes that occurred in the tunica media of the sinuses of Valsalva of the neoaortic roots in 9 patients who underwent reoperations for autograft failure. Their study highlighted that the pulmonary autograft remodeling with dilatation has a certain protein expression pattern. Interestingly, the protein expression in pulmonary autografts was very different from that observed in the normal aortic root and pulmonary artery. The greatest differences, however, were observed when the autografts were compared with the normal pulmonary arteries. The proteomic changes appear to occur in the extracellular matrix and cytoskeleton, suggesting a maladaptive remodeling of the autograft with progressive loss of elasticity and dilatation of the neoaortic root (Figure 1). The key differentially expressed proteins appeared to be thematically linked to cause extracellular matrix remodeling. The exact causation, however, is impossible to establish. The study raises more questions than it gives answers. Does the same “maladaptive” remodeling occur in nondilated autografts? Is such “maladaptive” remodeling merely a result of systemic pressure applied to the pulmonary autograft?
Figure 1Key proteomic changes in pulmonary autograft dilatation after the Ross operation are similar to those that occur in patients with nonsyndromic aortic aneurysms. MAGP, Microfibril-associated glycoprotein.
Embryologically, the aortic and pulmonary roots have the same truncal origin, and thus they likely have similar contents of collagen and elastin fibers and also similar densities of cells.
Human semilunar cardiac valve remodeling by activated cells from fetus to adult: implications for postnatal adaptation, pathology, and tissue engineering.
The fundamental question therefore is what drives genes to express “maladaptive” proteins in a setting of autograft failure. Potentially, there could be many factors responsible for autograft failure, including, but not limited to, age of patients, the nature of aortic valve disease, and technical aspects of the Ross procedure. It has been observed that the risk of autograft failure in younger children is less than that in older children, which may reflect the adaptive capability of autograft to remodel through the “normal” gene expression.
reported a mean age of 37 years for patients who underwent autograft explantation, which may reflect the age-related loss of adaptive capability of autograft in older patients.
Furthermore, it appears that patients with bicuspid aortic valve have a higher rate of autograft dysfunction.
Similarly, this may also be a reflection of the anomalous genes expression in the implanted autograft in this subgroup of patients. Importantly, the similar proteomic pathways are activated in patients with nonsyndromic thoracic aneurisms.
At present, neither the proteomics of nondilated pulmonary roots exposed to systemic pressure nor the causation of the “maladaptive” remodeling is fully understood. Nevertheless, it is not entirely inconceivable that the “-omic” technology may potentially evolve into a useful diagnostic tool to identify patients at risk for autograft failure. The current application of proteomics is more of a dream than a surgical reality. It is yet to be seen what dreams may come.
References
Chiriani A.
Faggian G.
Armato U.
Luciani G.B.
Maladaptive remodeling of pulmonary artery root autografts after Ross procedure: a proteomic study.
Human semilunar cardiac valve remodeling by activated cells from fetus to adult: implications for postnatal adaptation, pathology, and tissue engineering.
Pulmonary autograft root dilatation is the major long-term complication after Ross procedure and the leading cause for reoperation. However, the mechanisms underlying dilatation remain to be elucidated. This study analyzed the proteomic changes seen in the dilated pulmonary autograft compared with normal pulmonary artery and aorta tissues.
31746-5&id=fx1.jpg){kind=link}
31746-5&id=gr1.jpg){kind=link}