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Current Cardiology Reviews
ISSN: 1573-403X
Current Cardiology Reviews
Volume 2, Number 3, August 2006
Contents
Exercise and Ischemic Preconditioning Pp.
153-162
Antonio Crisafulli
[Abstract]
Matricellular Proteins in Myocardial Infarction
Pp. 163-171
Peter Huebener and Nikolaos G. Frangogiannis
[Abstract]
Inflammatory Markers in Coronary Artery Disease: Pathophysiological
Mechanisms, Prognostic and Therapeutic Implications
Pp. 173-184
Ignatios Ikonomidis, Kimon Stamatelopoulos, John Lekakis,
Dimitrios Th. Kremastinos
[Abstract]
A Therapeutic Target for Microvascular Complications in Diabetes:
Endothelium-Derived Hyperpolarizing Factor Pp. 185-191
Takayuki Matsumoto, Tsuneo Kobayashi and Katsuo Kamata
[Abstract]
Role of Nitric Oxide and Mitochondrial Nitric Oxide Synthase
in Energy Adaptive Responses Pp. 193-204
Jorge Guillermo Peralta and Juan José Poderoso
[Abstract]
Is Type D Personality Here to Stay? Emerging
Evidence Across Cardiovascular Disease Patient Groups Pp.
205-213
Susanne S. Pedersen and Johan Denollet
[Abstract]
High Sensitivity C-Reactive Protein (hsCRP):
A New Biochemical Marker of Atherosclerotic Vascular Disease
Pp. 215-225
Aylin Yildirir
[Abstract]
Fetal Origins of Cardiovascular Disease Pp.
227-236
Audra Wise, Shumei Yang and Lubo Zhang
[Abstract]
Abstracts
[Back to top]
Exercise and Ischemic Preconditioning
Antonio Crisafulli
There is growing clinical and epidemiological evidence
supporting the concept that regular exercise training reduces
the incidence of coronary events and increases the chance
of survival after myocardial infarction. This protection is
achieved through the reduction of many risk factors relating
to cardiovascular disease, such as high blood pressure, high
cholesterol, obesity etc. Moreover, exercise has been found
capable of reproducing the phenomenon known as ischemic preconditioning
(IP). This term identifies the capacity of short periods of
ischemia to render the myocardium more resistant to a subsequent
ischemic insult. Classically, the IP phenomenon refers to
the ability to limit the infarct size. However, IP is a complex
phenomenon which, along with infarct size reduction, can also
provide protection against ischemia- and reperfusion-induced
arrhythmia and myocardial stunning. There are several indications
demonstrating that exercise may directly induce preconditioning,
thus putting the heart in a protection status without the
need for a prior ischemia. It appears that exercise acts as
a physiological stress that induces beneficial myocardial
adaptive responses at cellular level. The purpose of the present
paper is to review the latest data on the role played by exercise
in inducing myocardial preconditioning.
[Back to top]
Matricellular Proteins in Myocardial Infarction
Peter Huebener and Nikolaos G. Frangogiannis
Matricellular proteins are extracellular matrix
proteins that do not play a direct structural role but act
contextually modulating cell function and activity. These
structurally diverse proteins include Thrombospondin (TSP)-1
and -2, tenascin-C and –X, Osteonectin/SPARC (Secreted
protein, acidic and rich in cysteine) and osteopontin (OPN).
Matricellular proteins show low level expression in normal
adult tissues, but are markedly upregulated in wound healing
and tissue remodeling. Our review examines our current knowledge
of the expression and role of the matricellular proteins in
the infarcted heart. TSP-1 and tenascin-C are upregulated
in the border zone of healing infarcts. TSP-1 null mice exhibit
enhanced and prolonged inflammation and extension of the inflammatory
infiltrate into the non-infarcted areas, suggesting a role
for TSP-1 in containment of the inflammatory response. These
defects are probably due to impaired TGF-β
activation and lead to increased adverse remodeling. OPN is
markedly upregulated in healing infarcts and is predominantly
localized in a subset of macrophages. OPN -/- mice show increased
left ventricular dilation and defective collagen deposition
in the infarct. SPARC is also markedly induced in experimental
models of infarction; however, its role in the healing process
remains unknown. Matricellular proteins play an important
role in the orchestration of the molecular events involved
in infarct healing by modulating a wide range of cellular
responses. Understanding the role of specific functional domains
of the matricellular proteins in infarct healing may result
in identification of novel therapeutic strategies aiming at
optimizing cardiac repair.
[Back to top]
Inflammatory Markers in Coronary Artery
Disease: Pathophysiological Mechanisms, Prognostic and Therapeutic
Implications
Ignatios Ikonomidis, Kimon Stamatelopoulos, John Lekakis,
Dimitrios Th. Kremastinos
Several inflammatory proteins intervene with endothelium
and haemostatic factors leading to plaque formation and rupture.
Of these, C-reactive protein (CRP), monocyte/macrophage colony-stimulating
factor (MCSF) and interleukin-6 (IL-6) promote atherogenesis
by inducing monocyte-macrophage activation, foam cell formation,
platelet activation, tissue factor expression, release of
other procoagulant cytokines or downregulation of atheroprotective
cytokines, namely interleukin 10 and transforming growth factor
b-1 (TGF-b1). CRP, MSCF and IL-6 are interrelated and have
been found increased in circulation in both chronic CAD and
acute coronary syndromes. IL-6 is also related to the extent
and duration of LV dysfunction following reversible myocardial
ischaemia. TGF-b1 has been found decreased in patients with
CAD and inversely related with MCSF. More importantly, increased
levels of CRP or MCSF and low levels of TGFb-1 predict adverse
cardiovascular events in CAD patients independently of traditional
risk factors. Moreover, in patients with chronic CAD, the
predictive value of MCSF is additive and beyond that of CRP
suggesting the need of a “multimarker approach”
in assessing cardiovascular risk. Although several therapeutic
strategies like vaccination against antigens promoting atherogenesis,
cyclooxygenase inhibitors (aspirin, coxibs), statins, and
ACE inhibitors may reduce the levels of these inflammatory
markers, the impact on cardiovascular risk resulting from
these changes is unknown.
Thus, inflammatory markers may serve as independent prognostic
markers as well as therapeutic targets.
[Back to top]
A Therapeutic Target for Microvascular
Complications in Diabetes: Endothelium-Derived Hyperpolarizing
Factor
Takayuki Matsumoto, Tsuneo Kobayashi and Katsuo Kamata
Vascular alterations in diabetes cause or contribute
to the etiology of microvascular complications such as nephropathy,
neuropathy, and retinopathy. The endothelium controls the
vascular smooth muscle tone through the production of vasodilator
mediators such as nitric oxide, prostacyclin, and a still-elusive
endothelium-derived hyperpolarizing factor (EDHF). Although
EDHF is a prominent vasodilator, particularly in smaller arteries,
little attention has been paid to the potential role of EDHF
responses in diabetes. EDHF function may involve the participation
of mediators, including several diffusible factors and non-diffusible
factors, (e.g., conduction of hyperpolarization via
myoendothelial gap junctions). Indeed, in several vessels,
cyclic adenosine 3’,5’-monophosphate (cAMP) facilitates
EDHF responses by enhancing electrotonic conduction via
gap junctions. It has been demonstrated that the alterations
in EDHF relaxation seen in mesenteric arteries from diabetic
rats may be attributable to an increase in phosphodiesterase3
(PDE3) activity, leading to a reduction in the action of cAMP,
and moreover the activity of protein kinase A (PKA) is decreased
in such arteries. Although an improvement in EDHF responses
has not been, as yet, the subject of any direct pharmaceutical
effort, increasing cAMP/PKA signaling (e.g., by inhibiting
PDE3 activity) has potential as an interesting therapeutic
target in diabetic microvascular disease.
[Back to top]
Role of Nitric Oxide and Mitochondrial
Nitric Oxide Synthase in Energy Adaptive Responses
Jorge Guillermo Peralta and Juan José Poderoso
Nitric oxide (.NO) regulates mitochondrial oxygen
uptake through reversible high-affinity binding to heme and
Cu2+ centers of
cytochrome oxidase, and sets adaptive responses to changes
in blood flow, O2 availability and hypoxia, thyroid
disorders, endotoxemia and cold adaptation. Moreover, subcellular
traffic of.NO synthases (NOS) participates in the adjustment
of mechanical cardiac efficiency. In isolated beating rat
hearts,.NO and bradykinin promote a dose-dependent decrease
of myocardial O2 uptake and coronary perfusion
pressure, without significant variations of the developed
left ventricular pressure. Also, in human hearts.NO from NOS
isoforms tunes mechanical performance. On these bases, NOS
traffic to mitochondria acquires physiological significance.
In liver and heart, mitochondrial NOS (mtNOS) was identified
as the neuronal isoform (nNOSα)
with postranslational modifications. This new class of NOS
spatial confinement leads cells to save energy under particular
circumstances. Likewise, thyroid status reciprocally regulates
mtNOS expression and.NO yield, while it linearly regulates
mitochondrial respiration and systemic oxygen uptake. In rats
exposed to cold, a clear contribution of.NO from mtNOS to
modulation of.VO2 and redistribution of energy
expenditure was reported. We conclude that.NOS traffic and
mtNOS activity are natural mechanisms to link mitochondria
and cardiovascular responses to environmental and endogenously
mediated challenges
[Back to top]
Is Type D Personality Here to Stay? Emerging
Evidence Across Cardiovascular Disease Patient Groups
Susanne S. Pedersen and Johan Denollet
The distressed personality (Type D) is
an emerging risk factor in cardiovascular disease (CVD) that
incurs a risk on par with left ventricular dysfunction in
patients with ischemic heart disease. Type D is defined as
the co-occurring tendencies to experience increased negative
emotions and to inhibit self-expression in social interactions.
Evidence is accumulating that Type D may also be a risk factor
for adverse outcome across CVD patient groups, including patients
undergoing revascularization with drug-eluting stent implantation
or bypass surgery, patients with heart failure, peripheral
arterial disease, and arrhythmia. In these patient groups,
Type D personality has been associated with a 2-5 fold increased
risk of adverse prognosis, impaired quality of life and symptoms
of anxiety and depression independent of traditional biomedical
risk factors, including disease severity. Although little
is known about the pathways responsible for the detrimental
effects of Type D on clinical outcome, the immune system and
health-related behaviors, such as smoking and non-compliance,
are likely candidates. Further research is warranted to investigate
whether Type D personality is here to stay as a risk factor
for CVD, but weighing current evidence on Type D against a
set of external criteria shows that Type D personality fulfills
the majority of these criteria. Importantly, Type D can easily
be assessed in clinical research and practice with the standardized
and validated DS14.
[Back to top]
High Sensitivity C-Reactive Protein (hsCRP):
A New Biochemical Marker of Atherosclerotic Vascular Disease
Aylin Yildirir
Despite the recent advances in the treatment of
atherosclerotic vascular disease, more effective measures
should be provided for the primary prevention in high-risk
individuals. Serious adverse vascular events can be seen in
individuals with low risk calculations based on standard cardiovascular
risk factors including age, sex, history of smoking, low density
lipoprotein, high density lipoprotein, diabetes and hypertension.
These findings suggest the necessity of additional risk parameters.
Recently, characterization of the clear association between
atherosclerosis and inflammation lead to the use of several
circulatory inflammatory markers for cardiovascular risk stratification.
Among these markers high-sensitivity CRP is the most studied
one.
There are several studies reporting the value of high-sensitivity
CRP in defining cardiac adverse events both in patients with
acute coronary syndromes and those without known cardiovascular
disease. Moderately elevated high-sensitivity CRP levels are
associated with increased cardiovascular event rates independent
from the other risk factors. High-sensitivity CRP adds more
information to the risk defined by lipid levels, so helps
to define the candidates for statin therapy. This review summarizes
high-sensitivity CRP, factors affecting high-sensitivity CRP,
its role in risk stratifications and suggestions for its clinical
use.
[Back to top]
Fetal Origins of Cardiovascular Disease
Audra Wise, Shumei Yang and Lubo Zhang
Human epidemiological studies have shown a clear
association of adverse intrauterine environment and an increased
risk of ischemic heart disease in later adult life. Although
adult lifestyle adds to the effects developed during intrauterine
life, compelling evidence indicates that the association of
ischemic heart disease with adverse intrauterine environment
does not reflect confounding variables linked to adult lifestyle.
It is suggested that epigenetic programming in the gene expression
pattern caused by adverse intrauterine environments at a critical
period of development in early life plays an important role
in the heart development, and its lifelong pathophysiological
consequences in the adult heart. Potential fetal programming
of adult disease has been shown in maternal undernutrition
and fetal exposure to glucocorticoids, hypoxia, alcohol, tobacco
smoking, and cocaine. Although early epidemiological studies
suggest that small body size at birth is associated with an
increased risk of death from ischemic heart disease in the
adult, it is becoming clear that fetal growth restriction
is not a prerequisite of adult disease. Recent animal studies
suggest that adverse intrauterine environments suppress fetal
cardiac function, alter cardiac gene expression pattern, increase
apoptosis of cardiomyocytes, cause a premature exit of the
cell cycle of cardiomyocytes and myocyte hypertrophy, and
result in an increase in susceptibility of the adult heart
to ischemia-reperfusion injury. This review discusses recent
epidemiological evidence in humans, as well as evidence from
studies in experimental animals, of an association of adverse
intrauterine environments and an increased risk of ischemic
heart disease in the adult, and the possible molecular mechanisms
of epigenetic programming involved in fetal gene expression
pattern, which is essential in explaining many fundamental
biological processes by which a variety of cardiovascular
dysfunctions and disease emerge and evolve.
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