title: Effect of dietary β carotene on cerebral aneurysm and subarachnoid haemorrhage in the brain apo E-/- mice.
abstract: Atherosclerosis will lead to stenosis/occlusion in the lumen of various arteries of living body. This can lead various conditions including myocardial infarction, cerebral infarction/aneurysm and peripheral artery disease. Ang II is believed to be an important regulatory peptide involved in maintaining cardiovascular homeostasis and pathogenesis of various cardiovascular diseases. Matrix metalloproteinase's (MMPs), adhesion molecules and plasminogen systems are involved in the inflammatory reaction of various blood vessels as well as pathogenesis of cerebro vasuclar disease in apo E(-/-) mice during angiotensin II injection. The present study analyses the role of ang II in development of cerebral aneurysm and also evaluated the mRNA levels of MMPs, adhesion molecules, plasminogen systems and peroxisome proliferators-associated receptors in the brain of apo E(-/-) mouse during the progression of cerebral aneurysm and ischemic conditions. Also, this study evaluates the role of dietary β carotene on cerebrovascular disease. Serum total cholesterol (TC), Low density lipoprotein (LDL) and triglyceride (TG) levels were significantly increased in angiotensin II treated animals and further β carotene supplementation reduces TC but does not affect the triglyceride and LDL levels. Circulating levels of macrophages were significantly increased in angiotensin treated animals and further beta carotene supplementation significantly reduced the circulating macrophages. Cerebro meningeous aneurysm, subarachnoid haemorrhage, multiple foci of infarction, necrosis and infiltration of inflammatory cells were observed in the cerebral hemispheres of ang II treated animals, however, infarction size were reduced and no aneurysm, inflammatory foci was observed in β carotene treated animals. Real time analysis showed down regulation of mRNA levels of MMP 2, uPA, PAI, PPAR-A, MCSF1 and up regulation of tPA and MCP-1 in the brain during the progression of cerebral aneurysm and β carotene supplementation to bring to normal expression levels of all the candidate genes for cerebrovascular diseases. Based on above results, Ang II may induced cerebral aneurysm, ischemia/infarction on brain through RAS system by down regulating the mRNA levels of MMP 2, uPA, PAI, PPAR-A, MCSF1 and up regulating tPA and MCP-1 and β carotene attenuates the disease condition and bring down to normal expression levels of above genes.
authors.affiliation: Small Animal Facility, Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India.
authors.forename: K
authors.initials: K
authors.lastname: Gopal
authors.forename: P
authors.initials: P
authors.lastname: Nagarajan
authors.forename: T Avinash
authors.initials: TA
authors.lastname: Raj
authors.forename: P
authors.initials: P
authors.lastname: Jahan
authors.forename: H S
authors.initials: HS
authors.lastname: Ganapathy
authors.forename: M J
authors.initials: MJ
authors.lastname: Mahesh Kumar
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D001057:Apolipoproteins E; D001921:Brain / Q000378:metabolism*; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects*; D002532:Intracranial Aneurysm / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D013345:Subarachnoid Hemorrhage / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology*; D019207:beta Carotene / Q000494:pharmacology*
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; D009419:Nerve Tissue Proteins; D014662:Vasoconstrictor Agents; D014815:Vitamins; D019207:beta Carotene; D000804:Angiotensin II