Age of Collagen in Intracranial Saccular Aneurysms

Abstract

Background and Purpose The chronological development and natural history of cerebral aneurysms (CA) remains incompletely understood. We used 14C birth dating of a main constituent of CAs, i.e. collagen type I, as an indicator for biosynthesis and turnover of collagen in CAs in relation to human cerebral arteries to further investigate this. Methods Forty-six ruptured and unruptured CA samples from 43 patients as well 10 cadaveric human cerebral arteries were obtained. The age of collagen, extracted and purified from excised CAs, was estimated using 14C birth dating and correlated with CA and patient characteristics, including the history of risk factors associated with atherosclerosis and potentially aneurysm growth and rupture. Results Nearly all CA samples contained collagen type I which was less than 5 years old, irrespective of patient age, aneurysm size, morphology, or rupture status. However, CAs from patients with a history of risk factors (smoking or hypertension), contained significantly younger collagen than CAs from patients with no risk factors (mean 1.6±1.2 years versus 3.9±3.3 years, respectively, p= 0.012). CAs and cerebral arteries did not share one dominant structural protein, such as collagen type I, which would allow comparison of their collagen turnover. Conclusions The abundant amount of relatively young collagen type I in CAs suggests that there is on-going collagen remodeling in aneurysms, which is significantly more rapid in patients with risk factors. These findings challenge the concept that cerebral aneurysms are present for decades and that they undergo only sporadic episodes of structural change.

The unruptured intracranial aneurysm treatment score: A multidisciplinary consensus

“…The merit of this model is that it accounts for many different factors that often influence clinical decisions but that were not well studied in previous observational studies, e.g., young age or long life expectancy, coexistent modifiable or nonmodifiable risk factors, coexistent morbidities, morphologic UIA features, or relevance of clinical symptoms related to UIAs. 5,10,11,13,24,25 Admittedly, the UIATS model requires more baseline characteristics, than the PHASES score, which makes its application slightly more time consuming. However, our results highlight that specialists in UIA research and treatment account for these factors in their decisionmaking and that these specialists have a high level of agreement about how to handle these factors for which data are currently incomplete or lacking.…”

Different stages of the evolution of cerebral aneurysms: joint analysis of mechanical test data and histological analysis of aneurysm tissue

“…Meanwhile, in many studies, a classification is made of ruptured and unruptured aneurysms according to various criteria: maximum stress, maximum strain, distribution of the direction of collagen fibers, etc. All these results are indicated at different stages of development of aneurysm tissue, which, as shown, continues to develop for even several years [11]. Despite numerous studies in this area, it becomes clear that the main trigger destabilising the body of the aneurysm is still not elucidated.…”

Growth and remodeling of load-bearing biological soft tissues

“…Hence, synthetic arterial cells must not only increase their production of collagen to increase wall thickness to restore wall stress toward normal in hypertension, they must further increase production to offset the increased loss of collagen. Altered rates of collagen turnover (production and removal) similarly appear to be critical in other cases of arterial disease, including aneurysms [32]. …”

“…It was suggested that mechanobiological stability could be the so far unknown biomechanical principle governing the continued enlargement of aneurysms, a hypothesis supported by comparisons with clinical and experimental evidence. Accelerated mass turnover is observed in aneurysms [32, 80] while individuals with stiffer vessels, such as diabetics [81, 82], have a lower risk for rupture. Moreover, in aneurysms (where the stress does in general not equal the homeostatic value) increased mass production or decreased degradation (corresponding to higher ${\mathit{k}}_{\sigma }^i$ in (15)) impairs further dilatation [38, 39].…”