Pathogenesis and Prevention of Stroke in Spontaneously Hypertensive Rats

Okamoto, Kozo; Hazama, Fumitada; Yamori, Yukio; Haebara, Hideyuki; Nagaoka, Akinobu

doi:10.1042/cs048161s

Cited by 76 publications

(94 citation statements)

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“…This left 95 studies (Set 5). A second Medline search was performed (9 November 2007) and 3 additional papers retrieved (Nishimura et al, 2006;Jesmin et al, 2007;Nishimura et al, 2007) giving a total of 98 studies (Set 6), the earliest from 1975 (Okamoto et al, 1975). A further three papers have been added in the final version of the manuscript (total = 101).…”

Section: Methodsmentioning

confidence: 99%

Doin vivoExperimental Models Reflect Human Cerebral Small Vessel Disease? a Systematic Review

Hainsworth

Markus

2008

J Cereb Blood Flow Metab

228

204

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Cerebral small vessel disease (SVD) is a major cause of stroke and dementia. Pathologically, three lesions are seen: small vessel arteriopathy, lacunar infarction, and diffuse white matter injury (leukoaraiosis). Appropriate experimental models would aid in understanding these pathologic states and also in preclinical testing of therapies. The objective was to perform a systematic review of animal models of SVD and determine whether these resemble four key clinicopathologic features: (1) small, discrete infarcts; (2) small vessel arteriopathy; (3) diffuse white matter damage; (4) cognitive impairment. Fifteen different models were included, under four categories: (1) embolic injuries (injected blood clot, photochemical, detergent-evoked); (2) hypoperfusion/ischaemic injury (bilateral common carotid occlusion/stenosis, striatal endothelin-1 injection, striatal mitotoxin 3-NPA); (3) hypertension-based injuries (surgical narrowing of the aorta, or genetic mutations, usually in the renin-angiotensin system); (4) blood vessel damage (injected proteases, endotheliumtargeting viral infection, or genetic mutations affecting vessel walls). Chronic hypertensive models resembled most key features of SVD, and shared the major risk factors of hypertension and age with human SVD. The most-used model was the stroke-prone spontaneously hypertensive rat (SHR-SP). No model described all features of the human disease. The optimal choice of model depends on the aspect of pathophysiology being studied.

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Section: Methodsmentioning

confidence: 99%

Doin vivoExperimental Models Reflect Human Cerebral Small Vessel Disease? a Systematic Review

Hainsworth

Markus

2008

J Cereb Blood Flow Metab

228

204

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“…11) Spontaneously hypertensive rat stroke-prone (SHRSP) is a widely used animal model for hypertension and stroke. 12) Iritani et al reported that the serum cholesterol level in SHRSP was low when compared with that in normotensive age-matched Wistar Kyoto rats (WKY). 13) We previously reported that the low serum cholesterol level in SHRSP as compared with WKY may be attributable to the reduced activity of MPD and not 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase.…”

Section: )mentioning

confidence: 99%

Purification and Characterization of Mouse Mevalonate Pyrophosphate Decarboxylase.

Michihara

Akasaki

Yamori

et al. 2002

Biological & Pharmaceutical Bulletin

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One of the first steps in the biosynthesis of cholesterol from acetic acid is catalyzed by mevalonate pyrophosphate decarboxylase (MPD). This decarboxylase catalyzes a bimolecular reaction between mevalonate 5-pyrophosphate (MVAPP) and ATP to form isopentenyl pyrophosphate, inorganic phosphate, adenosine-5Ј-diphosphate (ADP), and CO 2 .MPD has been purifed from various sources including yeast, 1,2) latex of Hevea brasiliensis, 3) pig liver, 4,5) rat liver, [6][7][8] and chicken liver. 9) Its properties in rat and chicken have been examined in detail. Toth and Huwyler reported cDNA sequences of MPD from human liver and yeast.10) The recombinant human enzyme is a homodimer of 43-kDa subunits with 400 amino acids. We recently established a procedure for the purification of MPD from the liver of rats fed a diet containing 5% cholestyramine and 0.1% pravastatin (CP diet) using chromatography and polyclonal antiserum raised against rat MPD. 8)Epidemiological studies have indicated a negative association between the serum cholesterol level and the incidence of cerebral hemorrhage in humans.11) Spontaneously hypertensive rat stroke-prone (SHRSP) is a widely used animal model for hypertension and stroke.12) Iritani et al. reported that the serum cholesterol level in SHRSP was low when compared with that in normotensive age-matched Wistar Kyoto rats (WKY). 13) We previously reported that the low serum cholesterol level in SHRSP as compared with WKY may be attributable to the reduced activity of MPD and not 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. 14) Moreover, we found that the decline in activity was caused by a reduction in the amount of enzyme in SHRSP.15) As described above, it is important to understand the mechanism of the decrease in MPD. We are also very interested in whether MPDknockout or MPD-reduced mice experience cerebral hemorrhage. However, information on MPD in normal mice is relatively scarce.In this paper, we describe a simple procedure for the purification of MPD from mouse liver, the properties of MPD, and a comparison of this MPD with counterparts from other animals. MATERIALS AND METHODSMaterials Pharmalyte 3-10 for isoelectric focusing and Western blotting detection kits were purchased from Amersham Pharmacia Biotech. Affigel 10 and 15 were obtained from Bio-Rad. RS-[ 3 H] mevalonolactone was purchased from Du Pont-New England Nuclear. Albumin from rat fraction V was purchased from Wako Chemicals. ddy Mice (8 weeks of age) were obtained from Shimizu Experimental Animals. All other chemicals were of reagent grade and purchased from commercial sources.Radioactive Assay The activities of the crude extract as well as the purified enzyme were measured according to the method of Sawamura et al.14) Unless otherwise indicated, the reaction mixture consisted of 100 mM Tris-HCl (pH 7.2), 5 mM ATP, 5 mM MgCl 2 , 10 mM NaF, Purification of MPD in RatsPurification of rat liver MPD was carried out as described by Michihara et al. 8)Preparation of an Affinity Column with Anti-rat MPD Antibody We...

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“…11,12) SHRSP has a lower serum cholesterol level than the normotensive Wistar Kyoto rat (WKY). 13) We previously indicated that the lower activity of MPD caused by the reduced amount of this enzyme was responsible for the reduced cholesterol biosynthesis in the liver of SHRSP.…”

mentioning

confidence: 99%

Mevalonate Pyrophosphate Decarboxylase in Stroke-Prone Spontaneously Hypertensive Rat Is Reduced from the Age of Two Weeks.

Michihara

Sawamura

Yamori

et al. 2001

Biological & Pharmaceutical Bulletin

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Pathogenesis and Prevention of Stroke in Spontaneously Hypertensive Rats

Cited by 76 publications

References 0 publications

Doin vivoExperimental Models Reflect Human Cerebral Small Vessel Disease? a Systematic Review

Doin vivoExperimental Models Reflect Human Cerebral Small Vessel Disease? a Systematic Review

Purification and Characterization of Mouse Mevalonate Pyrophosphate Decarboxylase.

Mevalonate Pyrophosphate Decarboxylase in Stroke-Prone Spontaneously Hypertensive Rat Is Reduced from the Age of Two Weeks.

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