Age of collagen in intracranial saccular aneurysms.
OBJECTIVE
The chronological development and natural history of cerebral aneurysms (CAs) remain incompletely understood. We used (14)C birth dating of a main constituent of CAs, that is, collagen type I, as an indicator for biosynthesis and turnover of collagen in CAs in relation to human cerebral arteries to investigate this further.


METHODS
Forty-six ruptured and unruptured CA samples from 43 patients and 10 cadaveric human cerebral arteries were obtained. The age of collagen, extracted and purified from excised CAs, was estimated using (14)C 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 <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 versus 3.9±3.3 years, respectively; P=0.012). CAs and cerebral arteries did not share a 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 an ongoing collagen remodeling in aneurysms, which is significantly more rapid in patients with risk factors. These findings challenge the concept that CAs are present for decades and that they undergo only sporadic episodes of structural change.
From the Department of Neurosurgery (N.E., K.B., H.-J.S., D.H.) and Institute of Forensic Medicine (C.M.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Institute for Physiological Chemistry and Pathobiochemistry, Westfalian Wilhelms-University, Münster, Germany (R.D., P.B.); Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, CA (B.A.B.); Department of Epidemiology, University of Iowa (J.C.T.); Department of Neurology, Mayo Clinic, Rochester, MN (R.D.B.); Division of Neurosurgery, St. Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (R.L.M.); and Department of Surgery, University of Toronto, Toronto, Ontario, Canada (R.L.M.). etminan@uni-duesseldorf.de.
Nima
N
Etminan
From the Department of Neurosurgery (N.E., K.B., H.-J.S., D.H.) and Institute of Forensic Medicine (C.M.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Institute for Physiological Chemistry and Pathobiochemistry, Westfalian Wilhelms-University, Münster, Germany (R.D., P.B.); Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, CA (B.A.B.); Department of Epidemiology, University of Iowa (J.C.T.); Department of Neurology, Mayo Clinic, Rochester, MN (R.D.B.); Division of Neurosurgery, St. Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (R.L.M.); and Department of Surgery, University of Toronto, Toronto, Ontario, Canada (R.L.M.).
Rita
R
Dreier
From the Department of Neurosurgery (N.E., K.B., H.-J.S., D.H.) and Institute of Forensic Medicine (C.M.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Institute for Physiological Chemistry and Pathobiochemistry, Westfalian Wilhelms-University, Münster, Germany (R.D., P.B.); Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, CA (B.A.B.); Department of Epidemiology, University of Iowa (J.C.T.); Department of Neurology, Mayo Clinic, Rochester, MN (R.D.B.); Division of Neurosurgery, St. Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (R.L.M.); and Department of Surgery, University of Toronto, Toronto, Ontario, Canada (R.L.M.).
Bruce A
BA
Buchholz
From the Department of Neurosurgery (N.E., K.B., H.-J.S., D.H.) and Institute of Forensic Medicine (C.M.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Institute for Physiological Chemistry and Pathobiochemistry, Westfalian Wilhelms-University, Münster, Germany (R.D., P.B.); Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, CA (B.A.B.); Department of Epidemiology, University of Iowa (J.C.T.); Department of Neurology, Mayo Clinic, Rochester, MN (R.D.B.); Division of Neurosurgery, St. Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (R.L.M.); and Department of Surgery, University of Toronto, Toronto, Ontario, Canada (R.L.M.).
Kerim
K
Beseoglu
From the Department of Neurosurgery (N.E., K.B., H.-J.S., D.H.) and Institute of Forensic Medicine (C.M.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Institute for Physiological Chemistry and Pathobiochemistry, Westfalian Wilhelms-University, Münster, Germany (R.D., P.B.); Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, CA (B.A.B.); Department of Epidemiology, University of Iowa (J.C.T.); Department of Neurology, Mayo Clinic, Rochester, MN (R.D.B.); Division of Neurosurgery, St. Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (R.L.M.); and Department of Surgery, University of Toronto, Toronto, Ontario, Canada (R.L.M.).
Peter
P
Bruckner
From the Department of Neurosurgery (N.E., K.B., H.-J.S., D.H.) and Institute of Forensic Medicine (C.M.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Institute for Physiological Chemistry and Pathobiochemistry, Westfalian Wilhelms-University, Münster, Germany (R.D., P.B.); Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, CA (B.A.B.); Department of Epidemiology, University of Iowa (J.C.T.); Department of Neurology, Mayo Clinic, Rochester, MN (R.D.B.); Division of Neurosurgery, St. Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (R.L.M.); and Department of Surgery, University of Toronto, Toronto, Ontario, Canada (R.L.M.).
Christian
C
Matzenauer
From the Department of Neurosurgery (N.E., K.B., H.-J.S., D.H.) and Institute of Forensic Medicine (C.M.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Institute for Physiological Chemistry and Pathobiochemistry, Westfalian Wilhelms-University, Münster, Germany (R.D., P.B.); Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, CA (B.A.B.); Department of Epidemiology, University of Iowa (J.C.T.); Department of Neurology, Mayo Clinic, Rochester, MN (R.D.B.); Division of Neurosurgery, St. Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (R.L.M.); and Department of Surgery, University of Toronto, Toronto, Ontario, Canada (R.L.M.).
James C
JC
Torner
From the Department of Neurosurgery (N.E., K.B., H.-J.S., D.H.) and Institute of Forensic Medicine (C.M.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Institute for Physiological Chemistry and Pathobiochemistry, Westfalian Wilhelms-University, Münster, Germany (R.D., P.B.); Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, CA (B.A.B.); Department of Epidemiology, University of Iowa (J.C.T.); Department of Neurology, Mayo Clinic, Rochester, MN (R.D.B.); Division of Neurosurgery, St. Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (R.L.M.); and Department of Surgery, University of Toronto, Toronto, Ontario, Canada (R.L.M.).
Robert D
RD
Brown
From the Department of Neurosurgery (N.E., K.B., H.-J.S., D.H.) and Institute of Forensic Medicine (C.M.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Institute for Physiological Chemistry and Pathobiochemistry, Westfalian Wilhelms-University, Münster, Germany (R.D., P.B.); Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, CA (B.A.B.); Department of Epidemiology, University of Iowa (J.C.T.); Department of Neurology, Mayo Clinic, Rochester, MN (R.D.B.); Division of Neurosurgery, St. Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (R.L.M.); and Department of Surgery, University of Toronto, Toronto, Ontario, Canada (R.L.M.).
Hans-Jakob
HJ
Steiger
From the Department of Neurosurgery (N.E., K.B., H.-J.S., D.H.) and Institute of Forensic Medicine (C.M.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Institute for Physiological Chemistry and Pathobiochemistry, Westfalian Wilhelms-University, Münster, Germany (R.D., P.B.); Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, CA (B.A.B.); Department of Epidemiology, University of Iowa (J.C.T.); Department of Neurology, Mayo Clinic, Rochester, MN (R.D.B.); Division of Neurosurgery, St. Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (R.L.M.); and Department of Surgery, University of Toronto, Toronto, Ontario, Canada (R.L.M.).
Daniel
D
Hänggi
From the Department of Neurosurgery (N.E., K.B., H.-J.S., D.H.) and Institute of Forensic Medicine (C.M.), Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Institute for Physiological Chemistry and Pathobiochemistry, Westfalian Wilhelms-University, Münster, Germany (R.D., P.B.); Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, CA (B.A.B.); Department of Epidemiology, University of Iowa (J.C.T.); Department of Neurology, Mayo Clinic, Rochester, MN (R.D.B.); Division of Neurosurgery, St. Michael's Hospital, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (R.L.M.); and Department of Surgery, University of Toronto, Toronto, Ontario, Canada (R.L.M.).
R Loch
RL
Macdonald
D000368:Aged; D000369:Aged, 80 and over; D002536:Cerebral Arteries / Q000378:metabolism* / Q000473:pathology*; D024042:Collagen Type I / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000473:pathology; D002532:Intracranial Aneurysm / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism
D024042:Collagen Type I
intracranial aneurysms; natural history; radiocarbon dating; risk factors