Novel Genetic Mechanisms for Aortic Aneurysms
- First Online:
- 156 Downloads
Aortic aneurysms occur in the thoracic and abdominal sections of the aorta and are a deadly late-age-at-onset disease with complex pathobiology. Currently, the number of published genome-wide analyses including microarray-based expression profiling, DNA linkage studies, and genetic association studies is still limited and it is difficult to make generalizations about the disease pathogenesis or genetic risk factors contributing to aortic aneurysms, but it appears that thoracic aortic aneurysms differ in many ways from abdominal aortic aneurysms. Characterization of diseases at the molecular level is likely to lead to more accurate diagnoses and the use of “genomic nosology” of disease. The biggest future challenge will be to translate the genomic information to the clinic and improve our understanding of the disease processes, help us to develop better diagnostic tools, and lead to the design of new ways to manage aortic aneurysms in the era of personalized medicine.
KeywordsAorta Aneurysm Embryology Embryologic origin Genetic risk factor DNA linkage analysis Genetic association study Sciatic artery Losartan Genomic nosology Abdominal aortic aneurysm Thoracic aortic aneurysm ANRIL Transforming growth factor-beta
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Beckman JA: Aortic aneurysms: pathophysiology, epidemiology, and prognosis. In Vascular Medicine. Edited by Creager MA, Dzau VJ, Loscalzo J. Philadelphia: Saunders Elsevier; 2006:543–559.Google Scholar
- 2.Beckman JA: Aortic aneurysms: clinical evaluation. In Vascular Medicine. Edited by Creager MA, Dzau VJ, Loscalzo J. Philadelphia: Saunders Elsevier; 2006:560–569.Google Scholar
- 18.von Meyenburg H: Ueber spontane Aortenruptur bei zwei Bruedern. Schwiez Med Wschr 1939, 20:976–979.Google Scholar
- 24.•• Guo DC, Pannu H, Tran-Fadulu V, et al.: Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet 2007, 39:1488–1493. This study mapped the seventh TAAD locus to 10q22-q24 in families with an autosomal dominant inheritance pattern for TAAD combined with livedo reticularis and iris flocculi and identified mutations in the gene for smooth muscle alpha-actin located in the candidate interval.CrossRefPubMedGoogle Scholar
- 28.Kuivaniemi H, Boddy AM, Lillvis JH, et al.: Abdominal aortic aneurysms are deep, deadly and genetic. In Aortic Aneurysms, New Insights Into an Old Problem. Edited by Sakalihasan N, Kuivaniemi H, Michel JB. Liège, Belgium: Liège University Press; 2008:299–323.Google Scholar
- 33.•• Helgadottir A, Thorleifsson G, Magnusson KP, et al.: The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet 2008, 40:217–224. This study was the first large genetic association study for abdominal aortic aneurysms. It demonstrated an association with a polymorphism on chromosome 9p21 and both AAAs and intracranial aneurysms. Interestingly, the same polymorphism had also been shown to be associated with myocardial infarction.CrossRefPubMedGoogle Scholar
- 35.•• Visel A, Zhu Y, May D, et al.: Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nature 2010, 464:409–412. This study provides the first indication of the mechanism by which the 9p21 risk variants exert their effect. It provides a clear role for the long noncoding RNA gene ANRIL in vascular SMC biology.CrossRefPubMedGoogle Scholar
- 41.ClinicalTrials.gov: Comparison of Two Medications Aimed at Slowing Aortic Root Enlargement in Individuals With Marfan Syndrome—Pediatric Heart Network. Available at http://www.clinicaltrials.gov/ct2/show/NCT00429364. Accessed February 8, 2010.