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Methionine diet-induced hyperhomocysteinemia accelerates cerebral aneurysm formation in rats
Yong Xu1, Ye Tian, Hui-Jie Wei
1Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052 PR China.
Insights
Hyperhomocysteinemia accelerates cerebral aneurysm formation in rats. This condition, caused by elevated homocysteine, may involve changes in vascular wall molecules, impacting aneurysm development.
Area of Science:
- Vascular Biology
- Neuroscience
- Inflammation Research
Background:
- Cerebral aneurysms (CA) pathophysiology involves chronic inflammation and endothelial damage.
- Elevated plasma homocysteine (Hcy) impairs vascular endothelium and is linked to atherosclerosis.
- The specific impact of hyperhomocysteinemia (HHcy) on cerebral aneurysm formation is not well understood.
Purpose of the Study:
- To investigate the effect of hyperhomocysteinemia on cerebral aneurysm formation.
- To determine the molecular changes in aneurysmal walls associated with HHcy.
Main Methods:
- Male Sprague-Dawley rats were subjected to surgical induction of CA with and without HHcy (high L-methionine diet).
- Aneurysm development was staged, and plasma Hcy levels were measured.
- Expression of VEGF, eNOS, iNOS, MMP-2, and MMP-9 in aneurysmal walls was analyzed.
Main Results:
- The methionine diet significantly increased plasma Hcy levels and accelerated CA formation.
- Expression of VEGF, iNOS, MMP-2, and MMP-9 was elevated in aneurysmal walls of rats with HHcy.
- These molecular changes correlated with increased CA formation.
Conclusions:
- Hyperhomocysteinemia accelerates cerebral aneurysm formation in a rat model.
- HHcy may influence CA development through altered expression of key vascular wall modeling molecules.
- This study provides insights into the molecular mechanisms underlying HHcy-induced CA formation.
Background And Purpose:
The pathophysiology of cerebral aneurysms (CA) is linked to chronic inflammation. Endothelial damage is one of the first changes in CA walls resulted from inflammation. It has been shown that increase in plasma homocysteine (Hcy) impairs vascular endothelium and correlates with the development of atherosclerosis. However, the effect of hyperhomocysteinemia (HHcy) on the formation of cerebral aneurysm remains unknown.
Methods:
Male Sprague-Dawley rats examined for developing cerebral aneurysms after surgical induction in the presence and absence of hypercysteinemia induced by a high L-methionine diet (1 g/kg/d). Aneurysms developed at the anterior cerebral-olfactory artery bifurcation were classified as 4 stages from no abnormality to saccular aneurysm. Plasma homocysteine levels and expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2), and MMP-9 in aneurysmal walls was examined and correlated with CA formation 3 months after surgery.
Results:
Methionine diet significantly increased plasma homocysteine levels, accelerates CA formation after ligation of the left common carotid artery. Expression of VEGF, iNOS, MMP-2, and MMP-9 in aneurysmal walls was also increased by methionine treatment.
Conclusion:
Hyperhomocysteinemia accelerates cerebral aneurysm formation, potentially through differential effects on expression of molecules critical for vascular wall modeling in a rat model.
