Arterial wall lesions form later and quicker than expected
12.04.2011
In a recent study, the newly appointed Professor at the University of Tartu Johan Björkegren and his team successfully determined the biological age of arterial wall lesions in patients suffering from cardiovascular disease. Arterial wall lesions limit the flow of blood to the brain and may lead to strokes. The findings of the study, published in the scientific online journal PLoS ONE, suggest that in most people, lesions form during a relatively short (3 5 years) period at an advanced age (60 or later).
“We presumed that the lesions would be substantially younger than the patients, who on average were 68 years old at the time of surgery. Yet we were surprised when we found that the average age of the lesions was even less than 10 years,” said Professor Johan Björkegren. “The whole idea is that lesion age can now be used to better understand the molecular underpinnings of these lesions. Biological age adds a new dimension to molecular biology that has gone unaddressed assuming that organs, healthy or diseased, have the same ages as its carrier, now we know that this is not true, at least not for vascular lesions,” Björkegren explained.
Another striking finding was that the variation of lesion age was low, suggesting that in most people, lesions form at an advanced age and relatively quickly – over a span of 3 5 years. If this is proved true, we may be able to slow the growth of arterial wall lesions and to prevent mini-strokes (Trans Ischemic Attacks or TIA) and strokes even in late stages of patients’ lives, at 60 years of age or possibly later.
The study was performed by collecting carotid plaques during carotid stenosis surgery at the Stockholm South General Hospital. Control samples were collected at University of Tartu Hospital by staff surgeon Arno Ruusalepp. The patients were admitted for surgery since their carotid lesions partly blocked the blood flow to the brain, causing symptoms of insufficient oxygen called Trans Ischemic Attacks (TIA) or mini-strokes that in some cases had also lead to strokes.
The plaques were carbon dated at Uppsala University in Sweden by using Accelerator Mass Spectrometry (AMS). As a result of extensive atomic bomb tests in the Pacific Ocean in the 1950s and 1960s, the atmospheric concentration of radioactive carbon 14 increased rapidly. This increase can now be used to date tissues in the human body.
The age of plaques was found to be associated with blood levels of insulin. More recently formed plaques were found to be more unstable than older plaques and therefore more likely to cause clinical complications, like mini-strokes and strokes.
“The correlations between low plaque age, higher insulin levels and instability are also consistent with our findings of gene activity where younger plaques were characterized with higher activity of genes related to immune responses and oxidative phosphorylation”, says Johan Björkegren. “However, this study is small and needs to be replicated in future, larger clinical studies before we can determine the exact roles of biological age for plaque stability and associated clinical events.”
Publication: ‘Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related to Levels of Plasma Insulin” Sara Hägg, Mehran Salehpour, Peri Noori, Jesper Lundström, Göran Possnert, Rabbe Takolander, Peter Konrad, Stefan Rosfors, Arno Ruusalepp, Josefin Skogsberg, Jesper Tegnér, Johan Björkegren, PLoS One, 2011.
Additional information: Professor Johan Björkegren, Professor of Pathological Anatomy, Department of Forensic Medicine and Pathology, University of Tartu,+46 (0)73-356 81 81, johan [dot] bjorkegren [ät] ut [dot] ee
or Arno Ruusalepp, Research Fellow of Pathological Physiology and Cardiovascular Surgery, Department of General and Molecular Pathology, Clinic of Cardiology, University of Tartu, +371 731 8432, arno [dot] ruusalepp [ät] kliinikum [dot] ee
“We presumed that the lesions would be substantially younger than the patients, who on average were 68 years old at the time of surgery. Yet we were surprised when we found that the average age of the lesions was even less than 10 years,” said Professor Johan Björkegren. “The whole idea is that lesion age can now be used to better understand the molecular underpinnings of these lesions. Biological age adds a new dimension to molecular biology that has gone unaddressed assuming that organs, healthy or diseased, have the same ages as its carrier, now we know that this is not true, at least not for vascular lesions,” Björkegren explained.
Another striking finding was that the variation of lesion age was low, suggesting that in most people, lesions form at an advanced age and relatively quickly – over a span of 3 5 years. If this is proved true, we may be able to slow the growth of arterial wall lesions and to prevent mini-strokes (Trans Ischemic Attacks or TIA) and strokes even in late stages of patients’ lives, at 60 years of age or possibly later.
The study was performed by collecting carotid plaques during carotid stenosis surgery at the Stockholm South General Hospital. Control samples were collected at University of Tartu Hospital by staff surgeon Arno Ruusalepp. The patients were admitted for surgery since their carotid lesions partly blocked the blood flow to the brain, causing symptoms of insufficient oxygen called Trans Ischemic Attacks (TIA) or mini-strokes that in some cases had also lead to strokes.
The plaques were carbon dated at Uppsala University in Sweden by using Accelerator Mass Spectrometry (AMS). As a result of extensive atomic bomb tests in the Pacific Ocean in the 1950s and 1960s, the atmospheric concentration of radioactive carbon 14 increased rapidly. This increase can now be used to date tissues in the human body.
The age of plaques was found to be associated with blood levels of insulin. More recently formed plaques were found to be more unstable than older plaques and therefore more likely to cause clinical complications, like mini-strokes and strokes.
“The correlations between low plaque age, higher insulin levels and instability are also consistent with our findings of gene activity where younger plaques were characterized with higher activity of genes related to immune responses and oxidative phosphorylation”, says Johan Björkegren. “However, this study is small and needs to be replicated in future, larger clinical studies before we can determine the exact roles of biological age for plaque stability and associated clinical events.”
Publication: ‘Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related to Levels of Plasma Insulin” Sara Hägg, Mehran Salehpour, Peri Noori, Jesper Lundström, Göran Possnert, Rabbe Takolander, Peter Konrad, Stefan Rosfors, Arno Ruusalepp, Josefin Skogsberg, Jesper Tegnér, Johan Björkegren, PLoS One, 2011.
Additional information: Professor Johan Björkegren, Professor of Pathological Anatomy, Department of Forensic Medicine and Pathology, University of Tartu,+46 (0)73-356 81 81, johan [dot] bjorkegren [ät] ut [dot] ee
or Arno Ruusalepp, Research Fellow of Pathological Physiology and Cardiovascular Surgery, Department of General and Molecular Pathology, Clinic of Cardiology, University of Tartu, +371 731 8432, arno [dot] ruusalepp [ät] kliinikum [dot] ee