Elastin Degradation in the Superficial Temporal Arteries of Patients with Intracranial Aneurysms Reflects Changes in Plasma Elastase

Connolly, E. Sander; Fiore, Amory J.; Winfree, Christopher J.; Prestigiacomo, Charles J.; Goldman, James E.; Solomon, Robert A.

doi:10.1097/00006123-199705000-00003

Cited by 30 publications

(11 citation statements)

References 36 publications

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“…High plasma elastase (PE) levels have been reported to play a role in systemic arterial elastin degradation seen in IA patients. These data also support the contention that elevated elastase levels are not the result of decreased protease inhibitor levels (133)(134)(135). Serum levels of a-1 antitrypsin (AAT), an elastase-specific inhibitor, are significantly lower in IA patients with SAH than in controls (136).…”

Section: Connective Tissues and Their Association With Iasupporting

confidence: 84%

“…Using an animal model, one study reported that the loss of elastic folds from the internal elastic lamina was observed in IA lesions, and the morphologic changes in the internal elastic lamina were considered to be responsible for aneurysm formation (145). There is also a report that IA patients have significantly elevated PE levels that are not the result of decreased levels of AAT (133). The difference in the expression level of elastin in cerebral vessels might also contribute to IA.…”

Section: Connective Tissues and Their Association With Iamentioning

confidence: 99%

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Molecular Genetics of Human Intracranial Aneurysms

Zhang

Claterbuck

2008

International Journal of Stroke

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Intracranial aneurysms (IAs) are the dilatations of blood vessels in the brain and pose potential risk of rupture leading to subarachnoid hemorrhage. Although the genetic basis of IAs is poorly understood, it is well-known that genetic factors play an important part in the pathogenesis of IAs. Therefore, the identifying susceptible genetic variants might lead to the understanding of the mechanism of formation and rupture of IAs and might also lead to the development of a pharmacological therapy. To elucidate the molecular pathogenesis of diseases has become a crucial step in the development of new treatment strategies. Although extensive genetic research and its potential implications for future prevention of this often fatal condition are urgently needed, efforts to elucidate the susceptibility loci of IAs are hindered by the issues bewildering the most common and complex genetic disorders, such as low penetrance, late onset, and uncertain modes of inheritance. These efforts are further complicated by the fact that many IA lesions remain asymptomatic or go undiagnosed. In this review, we present and discuss the current status of genetic studies of IAs and we recommend comprehensive genome-wide association studies to identify genetic loci that underlie this complex disease.

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Section: Connective Tissues and Their Association With Iasupporting

confidence: 84%

Section: Connective Tissues and Their Association With Iamentioning

confidence: 99%

Molecular Genetics of Human Intracranial Aneurysms

Zhang

Claterbuck

2008

International Journal of Stroke

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“…Thinning, fenestration and rupture of the inner elastic membrane and destruction of the elastic scaffold have been found at the site of aneurysm formation in histological studies [22, 23, 24, 25, 26]. Reticular fibers are diminished and irregularly distributed [8, 27, 28, 29].…”

Section: Discussionmentioning

confidence: 99%

Sterically Inhomogenous Viscoelastic Behavior of Human Saccular Cerebral Aneurysms

Tóth

Nádasy

Nyáry³

et al. 1998

J Vasc Res

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To clarify the mechanism leading to the development and rupture of intracranial aneurysms, tensile strength and viscoelastic parameters of 22 human saccular aneurysms were investigated. Meridional and circumferential strips from the thin and the thick part of the aneurysm sack and 18 control strips from the basilar artery of 8 patients with pathologies not affecting the cerebral arterial system were studied. The length of the strips was increased in 200-µm steps, while distending force was recorded. Tensile strength and viscoelastic parameters were computed. In both directions, tensile strength of thick strips was significantly lower than that of controls. In the meridional direction, tensile strength of thin strips was significantly larger than that of thick ones (14.5 ± 4.1 × 10⁶ vs. 7.5 ± 2.0 × 10⁶ dyn/cm², p < 0.05). In the circumferential direction, thin strips tore at lower strain values than thick ones (29 ± 4 vs. 55 ± 16%, p < 0.05). Viscoelastic parameters changed in parallel. In circumferential direction, values of thick and thin strips were significantly lower than those of controls. In the meridional direction, values of thin strips were significantly higher than those of the thick ones. These observations show that characteristic mechanical deterioration and steric inhomogeneities accompany the loss of smooth muscle cells and the derangement of connective tissue elements in the wall of intracranial aneurysms, which may explain certain steps in their initiation, enlargement and rupture.

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“…Estimates for the concentration of elastin in a developed cerebral aneurysm suggest that up to 90% of the elastin is lost (Connolly et al 1997). Similar results are found for the abdominal aorta (He andRoach 1993, MacSweeney et al 1992).…”

Section: Gandr Lawsmentioning

confidence: 59%

Impact of transmural heterogeneities on arterial adaptation

Schmid

Watton

Maurer

et al. 2009

Biomech Model Mechanobiol

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Recent experimental and computational studies have shown that transmurally heterogeneous material properties through the arterial wall are critical to understanding the heterogeneous expressions of constituent degrading molecules. Given that expression of such molecules is thought to be intimately linked to local magnitudes of stress, modelling the transmural stress distribution is critical to understanding arterial adaption during disease. The aim of this study was to develop an arterial growth and remodelling framework that can incorporate both transmurally heterogeneous constituent distributions and residual stresses, into a 3-D finite element model. As an illustrative example, we model the development of a fusiform aneurysm and investigate the effects of elastinous and collagenous heterogeneities on the stress distribution during evolution. It is observed that the adaptive processes of growth and remodelling exhibit transmural variations. For physiological heterogeneous constituent distributions, a stress peak appears in the media towards the intima, and a stress plateau occurs towards the adventitia. These features can be primarily attributed to the underlying heterogeneity of elastinous constituents. During arterial adaption, the collagen strain is regulated to remain in its homoeostatic level; consequently, the partial stress of collagen has less influence on the total stress than the elastin. However, following significant elastin degradation, collagen plays the dominant role for the transmural stress profile and a marked stress peak occurs towards the adventitia. We conclude that to improve our understanding of the arterial adaption and the aetiology of arterial disease, there is a need to: quantify transmural constituent distributions during histopathological examinations, understand and model the role of the evolving transmural stress distribution.

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Elastin Degradation in the Superficial Temporal Arteries of Patients with Intracranial Aneurysms Reflects Changes in Plasma Elastase

Cited by 30 publications

References 36 publications

Molecular Genetics of Human Intracranial Aneurysms

Molecular Genetics of Human Intracranial Aneurysms

Sterically Inhomogenous Viscoelastic Behavior of Human Saccular Cerebral Aneurysms

Impact of transmural heterogeneities on arterial adaptation

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