Novel Genetic Mechanisms for Aortic Aneurysms

Abstract

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.

Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants

“…These clinical measures and concepts all correlate with the rising evidence that the large heterogeneity of TAA and AAA is due to the different embryological origin of cell lineages in two portions of aorta [1,5]. Specifically, thoracic aorta originates from neuronal crests, while abdominal aorta derives from splanchnic mesoderm, as illustrated in Fig.…”

“…Both thoracic aortic (TAA) and abdominal aortic aneurysms (AAA), are also characterized to be silent and asymptomatic diseases and insidious in their progression [1,2]. Despite these common aspects, the two aorta pathologies show a significant heterogeneity in their prevalence, distribution along aorta length, age-at-onset, male:female ratio of disease susceptibility and pathophysiology, as reported in detail in Table 1 [3].…”

“…Underlying genetic factors contributing to two diseases also differ based on the site of the clinical manifestation, as well as their weight (see Fig. 1) [1,[5][6][7]. Accordingly, it has been evidenced that genetic determinants may influence AAA development.…”

Biglycan deficiency: Increased aortic aneurysm formation and lack of atheroprotection

“…The reason for the preferential increase in thoracic aortic aneurysms in biglycan-deficient mice is unclear. However, regional differences in aortic pathologies have been attributed to different embryonic origins of smooth muscle cells in different regions of the aortae[27, 28]; biglycan may be expressed to a different extent in these different smooth muscle lineages, which might account for these observations. Importantly, biglycan deficient mice in the present study (C57BL/6J background) developed classical breaks in aortic elastin upon angII infusions.…”

Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

“…Thus, MMP activation plays a central role in aorta age-related remodeling and consequently in pro-inflammatory aorta remodeling and stiffening, which are typical pathological entities of several aorta diseases. These include hypertension, atherosclerosis and aneurysm/dissection, showing regional specific onset associated with regional aorta embryologic origin, regional disease susceptibility and genetic factors associated with diseases [4,35,75].…”