Featured IAS Commentaries
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AUGUST
COMMENTARIES | SEPTEMBER COMMENTARIES
AUGUST 2008
Phenolics from Purple Grape, Apple, Purple Grape Juice, and Apple Juice Prevent
Early Atherosclerosis Induced by an Atherogenic Diet in Hamsters
Author: Jean-Max Rouanet
The beneficial health effect of high and regular
fruit consumption is an important point emphasized by recent
epidemiological studies. The protective effect afforded by
this dietary supply may be particularly beneficial for pathologies
such as coronary heart diseases [1-3] and some cancers [4].
Especially with regard to cardiovascular diseases (CVD), some
studies have shown a relationship between a reduced risk of
CVD and fruit consumption [2,3], but no indubitable evidence
was given. These protective effects could come from micro-nutrients
and micro-constituents, some of them being phenolic compounds
[5]. Most of these phenolics are powerful antioxidants [6]
and they might also offer protection against CVD [7]. When
not consumed raw, fruits undergo processing that can modify
these antioxidant properties in various ways, inducing antioxidant
loss, improvement of antioxidant properties of natural compounds,
formation of new compounds having antioxidant activity, formation
of compounds having pro-oxidant properties, or interactions
between different compounds [8]. Processing can also affect
the bioavailability of bioactive compounds. This is an important
aspect since only a small quantity of fruits is consumed in
the raw state, whereas the major part needs to be treated to
preserve quality as well as for safety and financial reasons.
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Effects of Renal Function and Metabolic Syndrome Components on Cardiovascular
and All-Cause Mortality
Author: Kuo-Liong Chien, M.D., Ph.D.
Impaired renal function and metabolic syndrome
have been associated with the risk of cardiovascular disease
(CVD) [1,2]. We investigated their roles in CVD and all-cause
death among ethnic Chinese population. Cross-sectional studies
have shown a significant relationship between chronic kidney
disease, metabolic syndrome, and atherosclerotic risk among
populations, but data on prospective cohorts for further cardiovascular
events were limited. In addition, the potential additive effects
of the chronic kidney disease and metabolic syndrome, after
considering the individual markers, were still unknown in ethnic
Chinese populations. The focus of the study was on renal function,
uric acid, and metabolic syndrome factors, particularly the
potential mediating effects among these risk factors on CVD
and all-cause mortality.
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Estrogen Receptor Alpha Gene and Cerebrovascular Disease
Authors: Sofia Markoula, M.D. and Ioannis Georgiou, Ph.D.
The role that reproductive steroids play in cerebrovascular
pathophysiology and ischemia is an important area of ongoing
investigation. Estrogens have vasoprotective properties against
atherosclerosis [1] that are mediated through activation of
specific estrogen receptors [2]. Vascular endothelial and smooth
muscle cells contain estrogen receptor alpha protein [1,3].
Estrogen receptor alpha is a ligand-activated transcription
factor influencing the regulation of cellular pathways and
believed to mobilize signals at the plasma membrane and in
the cytoplasm of the vessel wall cells.
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Prevalence of Metabolic Syndrome in Japanese
Type 2 Diabetic Patients and Its Significance for Chronic Vascular
Complications
Authors: Tokio Sanke, D.M., Ph.D.
The concept of the metabolic syndrome (MetS) as an independent
risk factor for cardiovascular disease is recognized worldwide
and several academic societies have defined their own diagnostic
criteria. Type 2 diabetes mellitus produces atherosclerotic
as well as microvascular changes as chronic complications and
is also recognized as an independent risk factor for cardiovascular
disease. Having more than one risk factor greatly increases
the risk for coronary heart disease [1].
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Carotid Intima-Media Thickness as a Predictor for Cardiovascular
Events in Patients with Rheumatoid Arthritis
Authors: Jet J.C.S. Veldhuijzen van Zanten, Aamer Sandoo, and
George D. Kitas
Rheumatoid arthritis (RA) is a chronic inflammatory
musculoskeletal disease, with principal symptoms of pain, stiffness,
and swelling of joints. Patients with RA are at increased risk
for cardiovascular disease, with almost half of all deaths
in RA due to cardiovascular disease [1]. Even though the underlying
mechanisms for this increased risk remain to be determined,
it is likely that the inflammation associated with RA not only
affects the joints but also the blood vessels [2]. Indeed,
patients with RA have been shown to have increased carotid
intima-media thickness (cIMT), which is a measurement of the
thickness of the carotid artery vessel wall. cIMT is a non-invasive
vascular assessment and it is thought to reflect structural
vessel changes at relatively advanced, yet sub-clinical, stages
of atherosclerosis. It is a good predictor for cardiovascular
events in the general population, especially in people with
low-grade inflammation assessed with C-reactive protein [3].
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Metabolic Syndrome in Mental Illness: Evidence and Way Out
Author: Sahoo Saddichha, BA, MBBS, DPM
Treatment in mental illness, especially schizophrenia, has
always been a challenge to clinicians. The advent of second-generation
antipsychotics or SGAs, as they are called, revolutionized
treatment by giving a wider choice of pharmaco-therapeutic
agents in treatment strategies. Unfortunately, these agents
of change have now been linked to a new epidemic of drug-induced
metabolic syndrome (MetS).
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Prevention of Metabolic Syndrome by Dietary
Manipulation
Author: Koji Nagao
Lifestyle-related diseases, such as obesity,
hyperlipidemia, atherosclerosis, type 2 diabetes, and hypertension,
are widespread and increasingly prevalent in industrialized
countries. Accompanied by the rapid increase in the number
of elderly people, this becomes a medical and a socioeconomic
issue. A clustering of metabolic disorders (in particular abdominal
obesity, hypertriglyceridemia, a low level of high density
lipoprotein cholesterol, hypertension, and high fasting glucose
levels) in an individual, defined as metabolic syndrome, is
known to increase cardiovascular morbidity and mortality. Although
the pathogenesis of metabolic syndrome is complicated and precise
details of the underlying mechanisms are not known, it has
been suggested that the quality of dietary lipids may be an
important modulator in terms of the risks associated with this
syndrome [1]. Animal studies and clinical trials have revealed
different effects of individual dietary lipids, such as n-3
polyunsaturated fatty acids (PUFAs), conjugated fatty acids
(CFAs), sterols, medium-chain fatty acids (MCFAs), diacylglycerols
(DAG), and phospholipids (PLs).
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A New Concept for Cellular Cholesterol Homeostasis
Authors: Yvonne
Lange and Theodore L. Steck
Most of the body burden of cholesterol is of
endogenous origin. Consequently, the way cells manage their
cholesterol impacts atherogenesis. Cells control their cholesterol
levels quite closely; we have determined, for example, that
the level of cholesterol in fibroblasts remains constant to
within ± 10% over weeks of cultivation. But how does
a cell know how much cholesterol it has and how much cholesterol
it needs; and how does it adjust the difference? The last of
these questions has been thoroughly explicated: multiple feedback
pathways respond in parallel to the level of cellular cholesterol
or the oxysterols derived therefrom [1, 2]. We now present
a new hypothesis concerning the first two questions: how cells
set their cholesterol requirement and sense deviations from
it [3,4].
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Heart Rate Reduction by Ivabradine Reduces Oxidative Stress, Improves Endothelial
Function and Prevents Atherosclerosis in Apolipoprotein E-Deficient Mice
Authors: Florian Custodis, Magnus Baumhäkel, Nils
Schlimmer, Franka List, Christoph Gensch, Michael Böhm,
and Ulrich Laufs
Epidemiological studies have shown that elevated
heart rate represents a risk factor for cardiovascular morbidity
both in primary prevention as well as in patients with hypertension,
coronary artery disease, and myocardial infarction [1-5]. Increased
heart rate and reduced heart rate-variability have been shown
to be associated with coronary plaque rupture and subclinical
inflammation in healthy middle-aged and elderly subjects [6,7].
Experimental data suggest that sustained elevations of heart
rate may play a role in the pathogenesis of coronary atherosclerosis
[8,9].
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The Effects of a Whole Grain-Enriched Hypocaloric
Diet on Cardiovascular Disease Risk Factors in Men and Women
with Metabolic Syndrome
Heather I. Katcher, Ph.D., R.D., Penny
M. Kris-Etherton,
Ph.D., R.D., and Richard S. Legro, M.D.
Many health benefits have been ascribed to whole
grains, especially in recent years [1-3]. A 30% reduced risk
of coronary artery disease and ischemic heart disease has been
observed in observational studies (the Nurse’s Health
Study [4], the Iowa Women’s Health Study [5], and the
Atherosclerosis Risk in Communities Study [6]) in individuals
who consume three or more servings of whole grains per day.
Several studies have demonstrated a lower BMI and reduced weight
gain over time in individuals who consume more whole grains
[7]. Whole grains are a good source of dietary fiber (both
soluble and insoluble), which favorably affects many physiological
processes such as lowering cholesterol and glucose levels,
and increasing satiety [8,9]. In addition to fiber, whole grains
deliver a package of many bioactive components to the diet
including antioxidants, phytochemicals, vitamins, and minerals
[9].
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Obesity-Hypertension: Emerging Concepts of
Neuroendocrine Dysregulation
Authors: Garry P. Reams, M.D., Daniel Villarreal,
M.D., FACC, FAHA, FIACS and Robert M. Spear, M.S.
The prevalence of obesity in the adult population
of the United States has risen markedly in the past three decades
and is presently greater than 30% [1]. This epidemic of obesity
represents a serious health hazard with significant morbidity
and mortality [1,2]. Indeed, obesity is associated with multiple
metabolic alterations, which in turn promote widespread atherogenesis
[1,3]. This cluster of disturbances, collectively known as
the metabolic syndrome, includes dyslipidemia, insulin resistance,
glucose intolerance, and hypertension, and may also be associated
with proinflammatory and prothrombotic states [3]. Although
it has become increasingly apparent that individuals with the
metabolic syndrome are at enhanced risk for cardiovascular
and renal disease, the precise etiology of this disorder, and
the underlying mechanisms that link its various components
remain incompletely defined.
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Atherosclerosis May Change an Angel to a Devil
Lessons from Anemia Treatment in Chronic Kidney Disease
Author:
Tetsuo
Shoji, M.D., Ph.D.
Patients with chronic kidney disease (CKD) are
at an elevated risk of death from cardiovascular disease (CVD)
[1]. The relative risk of death from coronary heart disease
is as high as 10 to 100 in patients with CKD stage 5 hemodialysis
patients. The raised risk for CVD can be attributable to changes
in the heart, blood vessels, blood, and others. Patients with
advanced CKD often suffer from cardiac hypertrophy, cardiac
dilatation, and cardiac failure. These are due partly to coronary
artery disease as a part of advanced systemic atherosclerosis,
and also to salt retention and volume overload associated with
impaired kidney function. Renal anemia, caused by erythropoietin
depletion, is believed to contribute to the increased CVD risk
by inducing ischemia of tissues, especially of myocardium and
brain, and also by promoting left ventricular hypertrophy in
response to increased cardiac output due to reduced hemoglobin
levels.
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Intracranial Atherosclerosis: An Underdiagnosed
Disease?
Authors: Mikael Mazighi and Pierre Amarenco
Intracranial atherosclerosis is considered to
be a severe but rare condition, occurring more frequently in
Asian, Afro-American, or Hispanic populations [1]. Overall,
intracranial atherosclerosis is considered to account for 5%
to 10% of ischemic strokes [1] and is associated with a high
risk of recurrent ischemic events as high as 22% per year [2,3].
The severity of intracranial atherosclerosis warrants an accurate
diagnostic work-up and a correct knowledge of the natural history
of the disease. Among the available imaging modalities, x-ray
angiography, MRA, CT angiography, and transcranial Doppler
ultrasonography, only image the residual lumen of intracranial
arteries and may fail to detect culprit intracranial plaques.
Only high-resolution MRI has proven capable of imaging the
arterial wall and detects symptomatic stenosis of intracranial
arteries, such as the middle cerebral artery (MCA) and basilar
artery [4]. These results suggest that intracranial atherosclerosis
prevalence is potentially underestimated due to lack of appropriate
diagnostic procedures. Recent data on autopsies of fatal stroke
patients emphasizes this hypothesis.
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Role of Cathepsin K in Structural Changes of the Brachiocephalic Artery during
Progression of Atherosclerosis in ApoE-Deficient Mice
Authors: Andriy O. Samokhin, Andre Wong, Paul Saftig, Dieter Brömme
Since the discovery of the potent collagenolytic
and elastolytic activities of cathepsin K several research
groups have studied its role in atherosclerotic lesion development
[1-3]. Extracellular matrix remodeling in the brachiocephalic
artery of ApoE-deficient mouse on a high fat diet has been
widely used as a model relevant for human atherosclerotic plaque
development [4]. Different compositions of the high fat diet
are used to accelerate the development of atherosclerosis.
The use of cholate in those diets is usually discouraged as
it might induce hepatic fibrosis with collagen accumulation
and the activation of proinflammatory genes [5-7]. However,
atherosclerosis is also recognized as a chronic inflammatory
disease and it was shown that the inclusion of cholate to an
atherogenic diet increases the destruction of elastic fibers
in the tunica media [8]. The link between dietary cholate,
collagen/elastin metabolism and increased arterial inflammation
prompted us to consider a high fat diet with 1% cholesterol
and 0.5% sodium cholate as a useful model to study the role
of cathepsin K in atheroma development in brachiocephalic arteries
of apoE-/- mice with potentially similar features to human
atherosclerotic plaques.
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Metabolic Syndrome: Criteria Validation in the Elderly
Authors: Stefania Maggi, M.D., Marianna Noale, Sc.D., and Gaetano
Crepaldi, M.D.
The metabolic syndrome (MetS) is the term used to describe
a clustering of metabolic and
physiologic risk factors for both type 2 diabetes mellitus
and atherosclerotic cardiovascular
diseases first described about 40 years ago [1]. Despite an
increasing number of works in the literature
dedicated to MetS, its underlying mechanism is still not completely
understood. Many
studies have shown that four of its components – obesity
(especially central obesity), impaired
glucose tolerance, atherogenic dyslipidemia (high levels of
triglycerides; small, dense low-density
lipoproteins; and low levels of high density lipoprotein cholesterol),
and hypertension - coexist
in the population to a greater degree than could be expected
by chance alone [2].
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Vascular Risks and Complications in Diabetes Mellitus: The
role of Helicobacter Pylori infection
Authors: Sherifa A. Hamed, Nabila F. Amine, Ghada
M. Galal, Shaaban R. Helal, Lubna M. Tag El-Din, Ola A.
Shawky,
Eman A. Ahmed, and Mohamed S. Abdel Rahman
It has been found that traditional risk factors
for atherosclerosis including age, gender, ethnicity, hypertension,
smoking, diabetes mellitus (DM), hyperlipidemia, and hyperhomocysteinemia
do not sufficiently explain all clinical and epidemiological
features of atherosclerosis as well as the incidence of its
related vascular complications. There is increasing evidence
that some atherogenic vascular risk factors (e.g. homeostatic
factors and lipids) are liable to be altered by inflammation
and infection by certain microbial agents including helicobacter
pylori (H. pylori) [1,2]. H. pylori is a gram negative micro-aerophilic
bacterium occurs naturally and inhabits the mucous layer of
the gastric epithelial cells.
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Atherosclerosisa Network of Genes
Driven By Environmental Pressures Filtered Through the Genetic
Make-Up of the Individual
Author:
Johan
Björkegren, M.D., Ph.D.
In the genomics era, we are finally in a position
to move from the assessment of individual candidate genes to
the simultaneous assessment of all genes involved in the development
of disease in organs and tissue [1]. New technologies developed
in parallel with the Human Genome Project make it possible
to capture close to all gene activities during the initiation
and progression of disease. Traditional statistics can now
be complemented with other analytical tools. In particular,
systems biological tools can be used to infer networks or otherwise
functionally associated genes in so-called modules from sets
of whole-genome data and thereby determine their role in disease
development [2].
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An Odyssey of Plaque to
Stroke: A Lipid Perspective
Authors:
Rao Muralikrishna Adibhatla and
James F. Hatcher
Stroke results from interruption of blood flow
to a region of the brain, which severely impairs the energy
supply. The majority of strokes result from either thrombolic
or embolic occlusion of primarily the middle cerebral artery.
Thrombolic stroke results from the formation of a clot or thrombus
in a cerebral artery that blocks blood flow at the site of
formation. Embolic stroke occurs when a cerebral artery is
blocked by a clot that formed elsewhere and was carried to
the brain through the circulation.
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Small Dense LDL Particles
and Metabolic Syndrome in a Sample of Middle-Aged Women. Findings
from Progetto
Atena
Authors: Marco Gentile, Ph.D., Salvatore
Panico, M.D., Fabrizio Jossa, M.D., Amalia Mattiello, M.D.,
Stefania Ubaldi, M.D., Gennaro
Marotta, M.D., Paolo Pauciullo, M.D., and Paolo Rubba, M.D.
The prevalence of the metabolic syndrome (MS)
is growing in the general population, particularly in women,
and has received increased attention in the past few years.
Increasing evidence indicates that the large population of
individuals with MS includes a heterogeneous group of disorders
with different cardiovascular risk [1].
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The
Importance of Gas6/Axl Anti-Apoptotic Signaling in Regulating
Vascular Calcification
Authors: Andrew Sage and Ann Canfield
Vascular calcification refers to the aberrant
development of cartilage and bone-like tissue and associated
mineralization of the extracellular matrix at distinct locations
within the vascular system: atherosclerotic plaques, the medial
layer of large and medium-sized arteries, and cardiac valves.
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Asymmetric Development of Peripheral Atherosclerosis
in Patients with Erectile Dysfunction: an
Ultrasonographic Study
Authors: C. Foresta and N. Caretta
Erectile dysfunction (ED), defined as the consistent
inability to obtain and maintain an erection for satisfactory
sexual intercourse, has a strong impact in the adult male population,
affecting approximately 20 million men in the U.S.A. [1] and
about 3 million men in Italy [2]. The pathophysiology of ED
is multifactorial, but it mainly involves a vascular disorder
related to a reduction of the endothelial function [3]. Increasing
evidence suggests the importance of ED as a reliable predictive
parameter of cardio-vascular diseases [4]. The co-morbidity
of ED with vascular disorders as coronary artery disease [5]
and carotid wall damage [6] have been exhaustively addressed,
but data on the arterial wall of lower-limbs in patients with
ED are still lacking.
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Impaired HDL-mediated Cholesterol Efflux in Metabolic Syndrome Subjects
Authors: Paul Nestel and Dmitri Sviridov
In a recent study of 25 men with metabolic syndrome,
we found that when their plasmas were incubated with macrophages
pre-labeled with radiocholesterol there was not the anticipated
positive correlation between HDL cholesterol (HDL-C) and cholesterol
efflux from the cells [1]. On the contrary the correlation
was negative and similar to that between efflux and LDL-C concentration.
Thus HDL, like LDL, appeared to donate more cholesterol to
the THP-1 macrophages (activated with LXR agonist) than was
accepted through efflux. When apoB lipoproteins were removed
the paradoxical relationship between influx and HDL-C remained
although the absolute efflux was reduced by the contribution
from apoB lipoproteins that can also serve as acceptors of
cellular cholesterol at least in vitro.
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