Abstract:
:A number of effective drugs have been developed through animal experiments, contributing to the health of many patients. In particular, the WHHL rabbit family (WHHL rabbits and its advanced strains (coronary atherosclerosis-prone WHHL-CA rabbits and myocardial infarction-prone WHHLMI rabbits) developed at Kobe University (Kobe, Japan) contributed greatly in the development of cholesterol-lowering agents. The WHHL rabbit family is animal models for human familial hypercholesterolemia, coronary atherosclerosis, and coronary heart disease. At the end of breeding of the WHHL rabbit family, this review summarizes the contribution of the WHHL rabbit family to the development of lipid-lowering agents and anti-atherosclerosis agents. Studies using the WHHL rabbit family demonstrated, for the first time in the world, that lowering serum cholesterol levels or preventing LDL oxidation can suppress the progression and destabilization of coronary lesions. In addition, the WHHL rabbit family contributed to the development of various compounds that exhibit lipid-lowering and anti-atherosclerotic effects and has also been used in studies of gene therapeutics. Furthermore, this review also discusses the causes of the increased discrepancy in drug development between the results of animal experiments and clinical studies, which became a problem in recent years, and addresses the importance of the selection of appropriate animal models used in studies in addition to an appropriate study design.
journal_name
J Atheroscler Thrombjournal_title
Journal of atherosclerosis and thrombosisauthors
Shiomi Mdoi
10.5551/jat.RV17038-2subject
Has Abstractpub_date
2020-02-01 00:00:00pages
119-131issue
2eissn
1340-3478issn
1880-3873journal_volume
27pub_type
历史文章,杂志文章abstract:AIM:Individuals with type 2 diabetes are at high risk for cardiovascular events; however, a modality that could reduce risk has not been fully evaluated. We examined the annual incidence rate of cardiovascular events in asymptomatic Japanese diabetic patients who underwent gated myocardial perfusion single-photon compu...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.13474
更新日期:2013-01-01 00:00:00
abstract:AIM:Cardiovascular events associated with hypertension often involve thrombosis. Increased platelet activity is one of the risk factors of cardiovascular diseases. Antithrombotic properties of antihypertensive agents are not fully characterized. Angiotensin II type 1 receptor blockers (ARBs) are widely used for the tre...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 临床试验,杂志文章
doi:10.5551/jat.14.31
更新日期:2007-02-01 00:00:00
abstract:AIM:The aim of this study was to investigate the clinical effect of planned endovascular therapy (EVT) for critical limb ischemia (CLI) patients with tissue loss. Although several rounds of EVT for CLI patients are required for complete wound healing, time required for complete wound healing depends on the wound severi...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.45344
更新日期:2019-03-01 00:00:00
abstract:AIM:Epicardial adipose tissue (EAT) has been suggested as a contributing factor for coronary atherosclerosis based on the previous cross-sectional studies and pathophysiologic background. However, a causal relationship between EAT and the development of non-calcified coronary plaque (NCP) has not been investigated. ME...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.36467
更新日期:2017-03-01 00:00:00
abstract:AIM:Factor VII activating protease (FSAP) is a plasma serine protease involved in hemostasis and remodeling processes. Increased levels of circulating FSAP during pregnancy and in women using oral contraceptives (OCs) indicate that the hormonal status critically influences FSAP expression. In this respect, the aim of t...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.9589
更新日期:2012-01-01 00:00:00
abstract::To determine the recent serum lipid levels and other serum variables in the general Japanese population and trends in their changes over the past 40 years, a nationwide survey of serum lipid levels was conducted in 36 institutes from various districts around Japan in 2000. The total number of subjects was 12,839, aged...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章,多中心研究
doi:10.5551/jat.12.98
更新日期:2005-01-01 00:00:00
abstract::We investigated the mechanism by which 7-ketocholesterol damages vascular smooth muscle cells and the protective effect of the hydroxymethyl glutary CoA reductase inhibitor, pravastatin on it. When 7-ketocholesterol (50 micromol/L) was added to cultured human vascular smooth muscle cells, the extent of cell detachment...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.9.65
更新日期:2002-01-01 00:00:00
abstract::We now have discovered and characterized a novel multi-domain protein and classified it as a member of the LDL receptor gene family. The approximately 250 kDa membrane protein, termed LR11, highly conserved in man, rabbit and chicken, contains a cluster of 11 LDL receptor ligand binding repeats, a group of 5 LDL recep...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章,评审
doi:10.5551/jat1994.4.20
更新日期:1997-01-01 00:00:00
abstract:AIM:Epicardial adipose tissue (EAT) is implicated in the development of coronary atherosclerosis.We sought to investigate the association between the EAT thickness and presence of multivessel disease (MV) in patients with acute myocardial infarction (AMI). METHODS:We enrolled 45 consecutive patients with AMI who under...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.26120
更新日期:2015-01-01 00:00:00
abstract:AIM:Changes in indexes of obesity, such as waist circumference (WC) and body mass index (BMI), may influence some glucose metabolism-related parameters in both obese and non-obese subjects. We have investigated the impact of changes in WC and in BMI on data related to glucose metabolism over a one-year period. METHODS...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.5959
更新日期:2010-12-26 00:00:00
abstract:AIM:Myriad biological effects of leptin may lead to broad therapeutic applications for various metabolic diseases, including diabetes and its complications; however, in contrast to its anorexic effect, the molecular mechanisms underlying adipopenic and glucose-lowering effects of leptin have not been fully understood. ...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.39552
更新日期:2017-11-01 00:00:00
abstract:AIM:Recent evidence suggests that small dense low-density lipoprotein (sd-LDL) particles are more atherogenic than large-LDL in spite of their lower cholesterol content. This study aimed to determine whether sd-LDL-cholesterol (sd-LDL-C) is superior to LDL-C as a biomarker of coronary heart disease (CHD). METHODS:LDL ...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.e572
更新日期:2008-10-01 00:00:00
abstract::Lecithin-cholesterol acyltransferase (LCAT) is an important enzyme involved in the esterification of cholesterol. Here, we report a novel point mutation in the LCAT gene of a 63-year-old female with characteristics of classic familial LCAT deficiency. The patient's clinical manifestations included corneal opacity, mil...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.8003
更新日期:2011-01-01 00:00:00
abstract:AIM:Angiotensin (Ang) II-induced abdominal aortic aneurysm (AAA) in apoE-deficient mice has been used as a model of human AAA, but it has been unclear why the progression of AAA continues after stopping the Ang II infusion. The involvement of vascular Ang II-forming enzymes in the progression of AAA was studied. METHO...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.e611
更新日期:2009-06-01 00:00:00
abstract::The purpose of the present study was to investigate the relationship between insulin resistance, sex hormones and sex hormone-binding globulin (SHBG) in regard to the serum lipid and lipoprotein profiles of 82 Japanese postmenopausal women. A multiple regression analysis for lipids, lipoproteins, and apoproteins as de...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat1994.8.14
更新日期:2001-01-01 00:00:00
abstract:AIM:Hypercholesterolemic patients with inflammation are at high risk for cardiovascular events. Statins exert anti-inflammatory action independent of their cholesterol-lowering action. This study sought to clarify whether statin therapy reduces inflammatory markers in hypercholesterolemic patients and to determine fact...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.3632
更新日期:2010-07-30 00:00:00
abstract:AIM:Resveratrol has been shown to mimic the beneficial effects of dietary restriction (DR). We previously reported that DR delays stroke onset and extends the lifespan in Stroke-Prone Spontaneously Hypertensive rats (SHRSP). Therefore, we examined whether resveratrol mimics DR and delays stroke onset in SHRSP. METHODS...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.27789
更新日期:2015-01-01 00:00:00
abstract:AIM:To evaluate the effect of statin therapy on the decrease of common carotid artery intima-media thickness (CCA-IMT) compared to placebo or usual care. METHODS:A systematic search of electronic databases (MEDLINE, EMBASE, and Cochrane Center Register) up to December 2011 was performed. Two reviewers independently de...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章,meta分析
doi:10.5551/jat.14001
更新日期:2013-01-01 00:00:00
abstract:AIM:Because the prevalence of hyperuricemia is lower in females than in males, the association between hyperuricemia and cardiovascular disease has been frequently reported in females. Increased serum uric acid levels are associated with the presence of cardiovascular risk factors such as hypertension, renal dysfunctio...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.33951
更新日期:2016-08-01 00:00:00
abstract:AIM:This study was designed to analyze microparticles (MPs) from endothelial cells (EMPs) and immune cells from healthy individuals and paitents with Takayasu arteritis (TA), and any possible relationships between MPs and TA acitivity. METHODS:MPs derived from the plasma of 51 subjects were analyzed, including 32 pati...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.45351
更新日期:2019-06-01 00:00:00
abstract:AIM:A new antibody reacted with an epitope in Lp(a) that has undergone oxidation treatment, but is not present in native Lp(a), was developed. Thus, we determined serum oxidized Lp(a) concentration in healthy volunteers, and coronary artery disease (CAD), diabetes mellitus (DM), and hypertensive patients. METHODS:We m...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.no224
更新日期:2009-08-01 00:00:00
abstract:AIM:Asymmetric dimethylarginine(ADMA) has recently been investigated as a risk marker for cardio- and cerebrovascular diseases. However, it is not currently known whether the ADMA levels are related to the risk of stroke in Japanese women. METHODS:We examined 192 Japanese women(mean age, 55±9 years, range, 40-80 years...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.22582
更新日期:2014-01-01 00:00:00
abstract::Blood lipid levels are highly heritable and modifiable risk factors for coronary artery disease (CAD), and are the leading cause of death worldwide. These facts have motivated human genetic association studies that have the substantial potential to define the risk factors that are causal and to identify pathways and t...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章,评审
doi:10.5551/jat.31393
更新日期:2016-01-01 00:00:00
abstract:AIM:Homocysteine is associated with increased arterial resistance and eventually causes luminal reduction. The purpose of the present study was to evaluate an association between the plasma concentration of total homocysteine (tHcy) and stenosis or occlusion of the internal carotid artery (ICA) in patients with ischemi...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.4796
更新日期:2010-09-30 00:00:00
abstract:AIM:Glucagon-like peptide-1 can reduce both postprandial plasma glucose (PG) and chylomicron (CM) levels in patients with type 2 diabetes. However, there have been no reports regarding the relationship between the postprandial metabolism of PG and CM. METHODS:Patients with type 2 diabetes who were admitted for glycemi...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章,随机对照试验
doi:10.5551/jat.32409
更新日期:2017-02-01 00:00:00
abstract:AIM:Soluble cell adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, E-selectin, and P-selectin, have been suggested to be associated with cardiovascular disease (CVD) risk; however, the nature and magnitude of the association between VCAM-1 and CVD risk is uncerta...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.38836
更新日期:2017-08-01 00:00:00
abstract:AIMS:Perilipin and adipophilin, PAT family proteins, play important roles in lipid metabolism. Although nonalcoholic fatty liver disease (NAFLD) is initiated by hepatocyte lipidation, little is known about the relationship between these proteins and hepatocellular injury. We investigated the expressions of perilipin an...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.2055
更新日期:2009-01-01 00:00:00
abstract::Cell degeneration and collagenosis are the main features in atherosclerotic plaque. We examined the effects of human low density lipoprotein (LDL) on cultured rabbit aortic smooth muscle cells (SMCs). Copper oxidized LDL (LDL+Cu) injured the SMCs more than did native LDL. Cytotoxicity of oxidized LDL was prevented by ...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat1994.1.53
更新日期:1994-01-01 00:00:00
abstract:AIM:CCL22, mainly synthesized by monocyte-derived alternative (M2) macrophages, belongs to the CC family of chemokines and is involved in monocyte migration and recruitment. We have previously investigated CCL22 and histamine in atherosclerosis. Here, we investigated the hypothesis that CCL22 is involved in atheroscler...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.44297
更新日期:2018-12-01 00:00:00
abstract:AIMS:Patients with chronic kidney disease (CKD) have a higher burden of cardiovascular morbidity and mortality than the general population. Endothelial dysfunction has been suggested to play a role in both glomerular filtration rate loss and cardiovascular damage. Thus, the present study aimed to evaluate the relations...
journal_title:Journal of atherosclerosis and thrombosis
pub_type: 杂志文章
doi:10.5551/jat.56424
更新日期:2020-09-02 00:00:00