The Association of ANRIL With Coronary Artery Disease And Aortic Aneurysms, How Far Does The Gene Desert Go?

BACKGROUND: Coronary artery disease (CAD) and aortic aneurysms (AA) are 2 cardiovascular diseases that share a multifactorial aetiology. The influence of family history and genetics on the 2 diseases separately and in association is well known, but poorly elucidated. This comprehensive review aims to examine the current literature on the gene ANRIL (antisense non-coding RNA in the INK4 locus) and its associations with CAD and AA. METHODS: A database search on OVID, PubMed and Cochrane to identify articles concerning single nucleotide polymorphisms (SNPs) associated with ANRIL and their respective incidences of, and impact on, CAD and AA across populations. RESULTS: Cohort studies across various ethnicities reveal that various ANRIL SNPs are significantly associated separately with CAD (rs1333040, rs1333049 and rs2383207) and AA (rs564398, rs10757278 and rs1333049), and that these SNPs are present in significant proportions of the population. SNP rs1333049 is significantly associated with both diseases, but is positively correlated with AAA and negatively correlated with CAD. This review further outlines several pathophysiological links via endothelial and adventitial cells, vascular smooth muscle cells and sense gene interaction, which may explain these genetic associations identified. CONCLUSION: Given the associations uncovered between ANRIL polymorphisms and CAD and AA, as well as the molecular mechanisms which may explain the underlying pathophysiology, ANRIL appears to be strongly linked with both diseases. ANRIL may hence have a future application in screening normal patients and risk stratifying patients with both diseases. Its role in linking the 2 diseases is yet unclear, warranting further studies.

Short- and long-term outcomes of aortic root-sparing repair and replacement in acute type A aortic dissection repair.

Acute type A aortic dissection is a surgical emergency with a high mortality rate if left untreated. Management of the aortic root in this setting constitutes an intricate decision-making framework, further complicated by the emergent nature of the dissection. There exists much controversy regarding pursuit of the aggressive aortic root replacement versus a conservative root-sparing repair, alongside considerations for valve-sparing root replacement. In this review, we critically appraise the current controversy in the literature considering the fate of the aortic root, discussing the aforementioned root interventions for which provides better outcomes for mortality and risk of re-intervention. Literature search was performed using electronic database through PubMed, Google scholar, and Embase focussing on studies reporting outcomes and re-intervention rates for these approaches. Limited by the heterogeneity in surgical strategy, with most studies being single-centred retrospective experiences, further fuel this ongoing debate. The literature reveals rather contrasting results whilst comparing root-sparing repair, versus the extensive root replacement; whilst some studies report no statistically significant difference, others show one superior over the other. There is greater consensus when considering risk of re-operation, with studies showing higher rates of re-operation in root-sparing group compared to replacement; however, many others show no statistically significant difference. In conclusion, the conflicting outcomes reported in the literature, with their inherent limitations, results in the current inability to reach a definitive answer. There remains support in the current literature for both approaches with much of the decision-making being surgeon-bound with many significant influencing factors on a case-by-case basis.