Differential Expression of Collagen Type V and XI α-1 in Human Ascending Thoracic Aortic Aneurysms

Toumpoulis, Ioannis K.; Oxford, Julia Thom; Cowan, Douglas B.; Anagnostopoulos, Constantine E.; Rokkas, Chris K.; Chamogeorgakis, Themistokles; Angouras, Dimitrios C.; Shemin, Richard J.; Navab, Mohamad; Ericsson, Maria; Federman, Micheline; Levitsky, Sidney; McCully, James D.

doi:10.1016/j.athoracsur.2009.04.030

Cited by 31 publications

(29 citation statements)

References 24 publications

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“…It is interesting, that S100A12 augments the levels of latent MMP-2 but had only minimal effect on the active form of MMP-2 when assessed by standard gelatin zymography. Accumulation of extracellular matrix proteins despite increased MMP proteins may seem at first contradictive, but recent studies utilizing human thoracic aneurysmal tissue have found the exact same findings, and support the hypothesis, that dysregulated synthesis of extracellular matrix could act indirectly to either induce or to further increase MMP synthesis and increase ECM degradation 30, 31…”

Section: Discussionmentioning

confidence: 83%

S100A12 Mediates Aortic Wall Remodeling and Aortic Aneurysm

Bowman

Wilk

Heydemann

et al. 2010

Circulation Research

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Rationale: S100A12 is a small calcium binding protein that is a ligand of RAGE (receptor for advanced glycation end products). RAGE has been extensively implicated in inflammatory states such as atherosclerosis, but the role of S100A12 as its ligand is less clear. Objective: To test the role of S100A12 in vascular inflammation, we generated and analyzed mice expressing human S100A12 in vascular smooth muscle under control of the smooth muscle 22␣ promoter because S100A12 is not present in mice. Methods and Results: Transgenic mice displayed pathological vascular remodeling with aberrant thickening of the aortic media, disarray of elastic fibers, and increased collagen deposition, together with increased latent matrix metalloproteinase-2 protein and reduction in smooth muscle stress fibers leading to a progressive dilatation of the aorta. In primary aortic smooth muscle cell cultures, we found that S100A12 mediates increased interleukin-6 production, activation of transforming growth factor ␤ pathways and increased metabolic activity with enhanced oxidative stress. To correlate our findings to human aortic aneurysmal disease, we examined S100A12 expression in aortic tissue from patients with thoracic aortic aneurysm and found increased S100A12 expression in vascular smooth muscle cells. Conclusions: S100A12 expression is sufficient to activate pathogenic pathways through the modulation of oxidative stress, inflammation and vascular remodeling in vivo. (Circ Res. 2010;106:145-154.)

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Section: Discussionmentioning

confidence: 83%

S100A12 Mediates Aortic Wall Remodeling and Aortic Aneurysm

Bowman

Wilk

Heydemann

et al. 2010

Circulation Research

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“…Concurrent hypertension in our patient might have been a precipitating factor for arterial rupture because altered biomechanical properties of arterial walls might produce a propensity for pressure‐induced dissection and/or rupture. Expression of type V collagen mRNA and protein is increased in ascending thoracic aortic aneurysms as compared to control aortic tissue [Toumpoulis et al, 2009]. While the pathophysiological mechanism underlying this observation is unknown, it is tempting to speculate that upregulation of type V collagen constitutes a molecular compensation to overcome disorganized aortic wall architecture.…”

Section: Discussionmentioning

confidence: 99%

Arterial rupture in classic Ehlers–Danlos syndrome with COL5A1 mutation

Borck

Beighton

Wilhelm³

et al. 2010

American J of Med Genetics Pt A

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The vascular type of Ehlers-Danlos syndrome (EDS IV) is associated with a high risk of life-threatening medical complications, including ruptures of large arteries, the intestine, and the uterus during pregnancy. An arterial rupture occurring in an individual with EDS is regarded as almost diagnostic of EDS IV, which is caused by heterozygous mutations in COL3A1. Here however, we report on a man with skin lesions typical of EDS, easy bruising and recurrent inguinal hernias who had a spontaneous rupture of the left common iliac artery at the age of 42 years but in whom we detected no COL3A1 mutation. As he clinically fulfilled the diagnostic criteria for classic EDS (EDS I), we sequenced the major EDS I gene COL5A1 and identified a heterozygous de novo nonsense mutation, c.3184C>T (p.R1062X). As, to the best of our knowledge, this is the first report of a patient with COL5A1 mutation-positive classic EDS and rupture of a large artery, we suggest that arterial rupture might be a rare complication of classic EDS. This finding has potential implications for genetic counseling and molecular genetic testing in Ehlers-Danlos syndrome.

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“…. On the contrary, collagen III was indicated to be down‐regulated in ascending aortic aneurysm wall . This may indicate that either increase or decrease in collagen level may weaken the aortic wall.…”

Section: Discussionmentioning

confidence: 94%

“…On the contrary, collagen III was indicated to be down-regulated in ascending aortic aneurysm wall. 34 This may indicate that either increase or decrease in collagen level may weaken the aortic wall. OPN, a highly phosphorylated sialoprotein, has been reported to be increased in AAA and involved in the pathogenesis of AAA, 35 also been reported to accelerate the growth of arterial aneurysm by inactivating TGFβ Signaling in Smad3-knockout mice.…”

Section: Discussionmentioning

confidence: 99%