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Current Vascular Pharmacology
ISSN: 1570-1611
Current Vascular Pharmacology
Volume 5, Number 2, April 2007
Contents
Inflammation, Sleep, Obesity and Cardiovascular
Disease Pp. 93-102
Michelle A. Miller and Francesco P. Cappuccio
[Abstract]
Bone Marrow Stem Cell Therapy for Myocardial Angiogenesis
Pp. 103-112
Hung-Fat Tse, Kai-Hang Yiu and Chu-Pak Lau
[Abstract]
Vascular Wall Shear Stress in Clinical Practice
Pp. 113-119
John Pantos, Efstathios Efstathopoulos and Demosthenes
G. Katritsis
[Abstract]
Antagonists of Activated Factor X and Thrombin: Innovative
Antithrombotic Agents Pp. 121-128
Massimo Franchini and Giuseppe Lippi
[Abstract]
Drug-Induced Pulmonary Hypertension in Newborns: A
Review Pp. 129-133
Paolo Silvani and Anna Camporesi
[Abstract]
Significance of Aspirin and Clopidogrel Resistance
in Patients Undergoing Percutaneous Coronary Interventions
Pp. 135-140
Jerzy Pregowski, Adam Witkowski and Dariusz Sitkiewicz
[Abstract]
Therapeutic Potential for Thyroid Hormone Receptor-β
Selective Agonists for Treating Obesity, Hyperlipidemia and
Diabetes Pp. 141-154
Gary J. Grover, Karin Mellström and Johan Malm
[Abstract]
Effects of Statins on Blood Pressure: A Review of
the Experimental and Clinical Evidence Pp. 155-161
Pantelis A. Sarafidis, Angeliki I. Kanaki and Anastasios
N. Lasaridis
[Abstract]
Cardiovascular Effects of Omega-3 Free Fatty Acids
Pp. 163-172
Francesco Biscione, Carlo Pignalberi, Alessandro Totteri,
Francesco Messina and Giuliano Altamura
[Abstract]
Abstracts
[Back to top]
Inflammation, Sleep, Obesity and Cardiovascular
Disease
Michelle A. Miller and Francesco P. Cappuccio
Evidence is emerging that disturbances in sleep and sleep
disorders play a role in the morbidity of chronic conditions.
However, the relationship between sleep processes, disease
development, disease progression and disease management is
often unclear or understudied.
Numerous common medical conditions can have an affect on sleep.
For example, diabetes or inflammatory conditions such as arthritis
can lead to poor sleep quality and induce symptoms of excessive
daytime sleepiness and fatigue. It has also been suggested
that poor sleep may lead to the development of cardiovascular
disease for which an underlying inflammatory component has
been proposed. It is therefore important that the development
and progression of such disease states are studied to determine
whether the sleep effect merely reflects disease progression
or whether it may be in some way causally related. Sleep loss
can also have consequences on safety related behaviours both
for the individuals and for the society, for example the increased
risk of accidents when driving while drowsy. Sleep is a complex
phenotype and as such it is possible that there are numerous
genes which may each have a number of effects that control
an individual’s sleep pattern.
This review examines the interaction between sleep (both quantity
and quality) and parameters of cardiovascular risk. We also
explore the hypothesis that inflammation plays an essential
role in cardiovascular disease and that a lack of sleep may
play a key role in this inflammatory process.
Aim: To review current evidence regarding
the endocrine, metabolic, cardiovascular and immune functions
and their interactions with regard to sleep, given the current
evidence that sleep disturbances may affect each of these
areas.
[Back to top]
Bone Marrow Stem Cell Therapy for Myocardial Angiogenesis
Hung-Fat Tse, Kai-Hang Yiu and Chu-Pak Lau
Despite the recent advances in medical therapy and coronary
revascularization procedures, coronary artery disease (CAD)
remains the major cause of morbidity and mortality in the
developing countries. In patients with severe CAD, persistent
myocardial ischemia in hibernated myocardium resulted in progressive
loss of cardiomyocytes with development of heart failure.
As a result, therapeutic approaches to enhance neovascularization
are being underwent intensive investigation. Recent experimental
studies have demonstrated adult bone marrow (BM) can induce
neovascularization in ischemic myocardium can improve heart
function. These findings have prompted the development of
different cellular transplantation approaches for heart diseases
refractory to conventional therapy after myocardial infarction.
Although the initial pilot clinical trials have shown potential
clinical benefit of BM therapy for therapeutic angiogenesis,
the long-term safety, the optimal timing and treatment strategy
remains unclear. Furthermore, in order to acquire more optimized
quality and quantity of BM derived stem cell for myocardial
regeneration, several issues remain to be addressed, such
as the development of a more efficient method of stem cells
identification, purification and expansion. Emerging, rationally
designed, randomized clinical trials are required to assess
the clinical implication of BM derived stem cells therapy
in treatment of CAD.
[Back to top]
Vascular Wall Shear Stress in Clinical Practice
John Pantos, Efstathios Efstathopoulos and Demosthenes
G. Katritsis
Wall shear stress is a fluid dynamic quantity that is gradually
emerging as a potentially important factor of coronary atherosclerosis.
Methods, therefore, of estimation of shear stress in the arterial
system are of clinical relevance. The purpose of this review
is to define wall shear stress, review the various methods
that have been used for its assessment in human circulation,
and examine the methodological limitations and applicability
of each method in clinical practice.
[Back to top]
Antagonists of Activated Factor X and Thrombin: Innovative
Antithrombotic Agents
Massimo Franchini and Giuseppe Lippi
Anticoagulant drugs are traditionally administered for the
prevention and treatment of thrombosis. Besides multi-targeted,
traditional anticoagulants, such as coumarins or heparins,
the search for the optimal antithrombotic efficacy to bleeding
risk ratio has prompted the development of a novel armamentarium
of anticoagulant drugs, which is expected to be introduced
in the market. These emerging drugs are mainly targeted to
suppress the propagation of the coagulation cascade (thrombin
burst), by direct thrombin inhibition or selective inhibition
of activated factor X. Therefore, thrombin or activated factor
X antagonists would produce an efficient anticoagulation while
minimizing the risk of bleeding, the most common adverse events
of conventional anticoagulants. No routine monitoring, favorable
form of administration and better compliance are additional
advantages of these innovative drugs, which are already in
advanced development or already licensed for clinical use.
The aim of this article is to provide an overview on the mechanisms
of action, clinical applications, cost-effectiveness and side
effects of these emerging anticoagulant strategies.
[Back to top]
Drug-Induced Pulmonary Hypertension in Newborns: A
Review
Paolo Silvani and Anna Camporesi
Persistent pulmonary hypertension (PPHN) is a disease characterised
by the disruption of the transition from fetal to neonatal
circulation with the persistence of high pulmonary vascular
resistances and right-to left shunting. This condition, occurring
in about 1-2 newborns per 1000 live births, causes severe
hypoxemia. Despite significant improvements in treatment,
the mortality of PPHN varies from 10 to 20 % of affected newborns.
Pulmonary hypertension is frequently observed in some cardiac
malformation and in congenital diaphragmatic hernia, in meconium
aspiration syndrome, neonatal sepsis, podalic presentation
and male sex. Maternal risk factors are tobacco smoking, cesarean
section, low socioeconomic conditions, diabetes and urinary
infections. Another predisposing condition is antenatal or
postnatal exposure to some drugs. The medications involved
in drug-induced pulmonary hypertension and the mechanisms
involved are reviewed.
[Back to top]
Significance of Aspirin and Clopidogrel Resistance
in Patients Undergoing Percutaneous Coronary Interventions
Jerzy Pregowski, Adam Witkowski and Dariusz Sitkiewicz
Dual antiplatelet therapy (aspirin plus clopidogrel) is mandatory
in patients treated with coronary stent implantation. This
strategy is highly effective in prevention of stent thrombosis
until its struts are covered with endothelium. However, a
substantial number of patients still suffer from recurrent
ischemic coronary events despite adequate antiplatelet therapy.
These events fall into three categories: stent thrombosis,
in stent restenosis and events related to other non-stented
coronary lesions. Some data suggest that beside other local
and systemic factors resistance to aspirin and clopidogrel
may be a possible cause of stent thrombosis and ischemic events
in patients after coronary interventions.
Several mechanisms of antiplatelet drug resistance have been
reported including poor compliance, interactions with other
drugs, genetic polymorphism or increased platelet turnover.
More research is needed to adequately assess the clinical
significance and prognostic value of antiplatelet drug resistance
detected by laboratory tests in patients undergoing percutaneous
intervention.
We review published data on mechanisms and the clinical significance
of aspirin and clopidogrel resistance in patients after coronary
interventions.
[Back to top]
Therapeutic Potential for Thyroid Hormone Receptor-β
Selective Agonists for Treating Obesity, Hyperlipidemia and
Diabetes
Gary J. Grover, Karin Mellström and Johan Malm
Obesity and metabolic syndrome are increasing dramatically
worldwide, contributing to cardiovascular morbidity and mortality.
There are currently few safe and efficacious therapeutics
for obesity and most strategies are focused on appetite suppression.
Thyroid hormones reduce adiposity via increased metabolic
rate, but unfortunately they cause large changes in metabolic
rate and direct cardiac acceleration, making them useless
for treating obesity. Thyroid hormone receptors (TRs) work
as transcription factors and two subtypes exist: TRα
and TRβ.
TRα
mediates tachycardia and much of the metabolic rate effect,
while TRβ
mediates cholesterol and TSH lowering effects of thyroid hormones.
TRβ
activation modestly increases metabolic rate such that a therapeutic
window of 5-10 fold increases in metabolic rate can be seen
without tachycardia. This was initially studied in TRα1-/-
mice. Recent structure activity work has resulted in the discovery
of several TRβ
selective thyromimetics such as KB-141. Studies with KB-141
show that it has a 10-fold window in which therapeutic increases
in metabolic rate are seen without tachycardia or cardiac
hypertrophy. This agent lowers cholesterol in rats and primates.
In primates, KB-141 causes significant weight and cholesterol
reduction in addition to the independent risk factor Lp(a).
These effects were seen without any effect on heart rate,
unlike thyroid hormone (T3). Further work with
TRβ
selective agents is warranted and recent work suggests the
possibility of developing compounds that selectively penetrate
different tissues which may have an even more desirable therapeutic
window. Selective thyromimetics, therefore, may be useful
as adjunctive therapy to appetite suppressants along with
exercise and diet restriction.
[Back to top]
Effects of Statins on Blood Pressure: A Review of
the Experimental and Clinical Evidence
Pantelis A. Sarafidis, Angeliki I. Kanaki and Anastasios
N. Lasaridis
The “pleiotropic” effects of statins have been
the centre of a considerable research activity. Among the
numerous experimental and clinical studies of this field,
some focused on the effects of statins on blood pressure (BP),
while others reported data on BP together with other parameters.
Some of the animal or human studies do not show an association
between statin treatment and BP changes, whereas others usually
report mild but significant reductions. Among the latter,
all clinical studies using ambulatory BP recordings show a
significant drop in both systolic and diastolic BP in hypertensive
patients. In addition, accumulating evidence has identified
a number of statin actions that may be involved in BP lowering.
Overall, current evidence suggests that statins can be associated
with a mild beneficial effect on BP, but further research
is needed to clarify the exact magnitude of this action, as
well as its clinical relevance.
[Back to top]
Cardiovascular Effects of Omega-3 Free Fatty Acids
Francesco Biscione, Carlo Pignalberi, Alessandro Totteri,
Francesco Messina and Giuliano Altamura
Omega-3 fatty acids are essential substances for
the development and function of human organism. They cannot
be synthesized in humans, and consequently have to be acquired
from food, almost exclusively from fish. Omega-3 fatty acids
exert potent anti-inflammatory and anti-atherosclerotic actions
by interfering with the metabolism of arachidonic acid, modifying
lipid composition (mainly lowering triglycerides), improving
hemodynamics and reducing cardiac hypertrophy. Recently, clinical
and experimental studies demonstrated an anti-arrhythmic effect
and a significant impact on survival after myocardial infarction
(MI). It follows that omega-3 fatty acids have been widely
accepted for clinical use in patients with dyslipidemia or
with atherosclerotic disease and in survivors of acute MI.
This review briefly explores the metabolic mechanisms and
the clinical effects of this class of substances and considers
their use in patients with cardiovascular disease.
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