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Current Vascular Pharmacology
ISSN: 1570-1611
Current Vascular Pharmacology
Volume 6, Number 3, July 2008
Contents
Editorial:
Cardiovascular Risk Factor Modification: A sine qua non
in the Manage-ment of Vascular Surgery Patients
Pp. 154-157
Matrix Metalloproteinases in Venous Tissue Remodeling
and Varicose Vein Formation Pp. 158-172
Joseph D. Raffetto and Raouf A.
Khalil
[Abstract]
Screening Haemostasis – Looking for Global
Assays: The Overall Haemostasis Potential (OHP) Method –
A Possible Tool for Laboratory Investigation of Global Haemostasis
in Both Hypo- and Hypercoagulable Conditions Pp.
173-185
Aleksandra Antovic
[Abstract]
The Role of Intravenous Dihydropyridine Calcium Channel
Blockers in the Perioperative Management of Patients Undergoing
Coronary Artery Bypass Surgery Pp. 186-194
Ali Khoynezhad, Paul P. Dobesh, Zachary Stacy
and Ziba Jalali
[Abstract]
Endothelin-1 Actions on Vascular Smooth Muscle Cell
Functions As a Target for the Prevention of Atherosclerosis
Pp. 195-203
Peter J. Little Melanie E. Ivey and
Narin Osman
[Abstract]
The Role of the Methoxyphenol Apocynin, a Vascular
NADPH Oxidase Inhibitor, as a Chemopreventative Agent in the
Potential Treatment of Cardiovascular Diseases Pp.
204-217
Jingjing Yu, Michel Weiwer, Robert J. Linhardt
and Jonathan S. Dordick
[Abstract]
Impact of Traditional Therapies and Biologics
on Cardiovascular Diseases in Rheumatoid Arthritis Pp.
218-227
Jean-Frédéric Boyer, Alain
Cantagrel and Arnaud Constantin
[Abstract]
Amiodarone Hepatotoxicity Pp. 228-236
Mohamed Babatin, Samuel S. Lee and P.
Timothy Pollak
[Abstract]
Abstracts
[Back to top]
Editorial:
Cardiovascular Risk Factor Modification: A sine qua non
in the Manage-ment of Vascular Surgery Patients
[Back to top]
Matrix Metalloproteinases in Venous Tissue Remodeling
and Varicose Vein Formation
Joseph D. Raffetto and Raouf A.
Khalil
Matrix metalloproteinases (MMPs) play a major role in
extracellular matrix (ECM) turnover under both physiological
and pathological conditions. Studies on venous tissues from
experimental animals and humans identified several MMP subtypes,
and showed significant changes in the expression and activity
of specific MMPs during vein wall remodeling. Also, significant
research has focused on the role of MMPs in chronic venous
disease (CVD) and varicose vein formation in the lower extremities
and their progression to thrombophlebitis and venous leg ulcer.
Several hypotheses have been forwarded regarding the pathophysiological
mechanisms underlying the relation between MMPs and the formation,
progression and complications of varicose veins. The effects
of MMPs on ECM degradation could result in significant venous
tissue remodeling and degenerative and structural changes
in the vein wall, leading to venous dilation and valve dysfunction.
MMPs may also induce early changes in the endothelium and
venous smooth muscle function in the absence of significant
ECM degradation or structural changes in the vein wall. In
addition, evidence suggests increased activity of MMPs in
the advanced stages of chronic venous insufficiency (CVI)
associated with skin changes and leg ulceration as well as
in the wound fluid environment. Several pharmacological therapies
and surgical strategies are being utilized in the management
of varicose veins, with variable success and recurrence rates.
Inhibition of MMPs may represent a novel therapeutic intervention
to limit the progression of varicose veins to CVI and leg
ulceration.
[Back to top]
Screening Haemostasis – Looking for Global Assays:
The Overall Haemostasis Potential (OHP) Method – A Possible
Tool for Laboratory Investigation of Global Haemostasis in
Both Hypo- and Hypercoagulable Conditions
Aleksandra Antovic
A broad spectrum of global haemostatic assays has recently
been developed and modified in an attempt to overcome the
drawbacks of classical screening tests used for evaluation
of coagulation and fibrinolysis. The Overall Haemostasis Potential
(OHP) assay is one of such assays. The assay is based on repeated
spectrophotometric registration of fibrin-aggregation in citrated
plasma, to which small amounts of exogenous thrombin, tissue
type plasminogen activator and calcium chloride have been
added. The area under the fibrin aggregation curve which then
develops is calculated and is the laboratory parameter used
for OHP determination. The Overall Coagulation Potential (OCP)
and Overall Fibrinolytic Potential (OFP) are supplementary
parameters of OHP, providing details of underlying changes
in coagulation and/or fibrinolysis. The sensitivity of the
assay for detecting hypercoagulation in normal pregnancy,
in preeclampsia, some thrombophilias, coronary heart disease,
diabetes, stroke and vascular surgery has been evaluated.
Since the assay can monitor haemostasis balance in the sample,
it may serve as a laboratory tool to determine hypocoagulation,
especially in patients with haemophilia A or B. Preliminary
findings also indicate that the OHP assay may be useful in
the monitoring of anticoagulant treatments. Larger controlled
clinical studies are, however, mandatory before a definite
conclusion about the usefulness of the method can be drawn.
[Back to top]
The Role of Intravenous Dihydropyridine Calcium Channel
Blockers in the Perioperative Management of Patients Undergoing
Coronary Artery Bypass Surgery
Ali Khoynezhad, Paul P. Dobesh, Zachary Stacy
and Ziba Jalali
The pharmacology characteristics of dihydropyridine calcium
channel blockers (CCB) make them an attractive antihypertensive
medication for use in the perioperative setting of coronary
artery bypass graft (CABG) surgery. They lack the negative
inotropic, negative chronotropic, and negative bathmotropic
effects of phenylalkylamine and benzothiazepine CCB that limit
the use in patients with heart failure or patients with bradyarrythmias.
With the aging population and significant rise in the prevalence
of heart failure, the use of dihydropyridine CCB as antihypertensive
medication after CABG surgery has become more common. Furthermore,
intravenous dihydropyridine CCB are being used in the perioperative
setting as vasodilatory agents after radial artery harvesting
for total arterial coronary revascularization.
We review the pharmacological effects of intravenous dihydropyridine
CCB, analyze the literature, and comment on the consequences
in modern clinical practice.
[Back to top]
Endothelin-1 Actions on Vascular Smooth Muscle Cell
Functions As a Target for the Prevention of Atherosclerosis
Peter J. Little Melanie E. Ivey and
Narin Osman
The formation and progression of atherosclerotic plaques
followed by rupture, thrombus formation and vessel blockage
leads to ischemic tissue damage and the clinical condition
underlying most cardiovascular disease. Therapeutic agents
for the prevention of atherosclerosis have all targeted epidemiologically
identified and relatively easily measured risk factors (e.g.
lipids and blood pressure). This strategy has proven somewhat
effective but is of less than optimal efficacy as rates of
cardiovascular disease remain high. Treatment targeting the
mechanisms of atherosclerosis in the vessel wall is a conceptually
attractive proposition to complement the risk factor directed
strategy. Vascular smooth muscle cells (VSMC) are the major
cellular component of the vascular media and migration and
proliferation leads to the formation of the neointima the
development of which renders the vessels particularly sensitive
to atherosclerosis. Numerous hormones and growth factors act
on VSMC to cause migration, proliferation and the secretion
of extracellular matrix and modulation or dysfunction of these
processes is the most likely cause of atherosclerosis. Endothelin
1 (ET 1) is a 21 amino acid peptide that acts on 7 transmembrane
G protein coupled receptors to elicit a plethora of responses
that can modulate the behaviour of VSMCs and thus impact on
the development of atherosclerosis. ET 1 is elevated in atherosclerotic
plaques. People with diabetes have accelerated atherosclerosis
and also show elevated plasma levels of ET 1. This review
addresses the actions of ET 1 on VSMC and the signalling pathways
through which it mediates its effects as the latter represent
potential therapeutic targets for the prevention of atherosclerosis.
[Back to top]
The Role of the Methoxyphenol Apocynin, a Vascular
NADPH Oxidase Inhibitor, as a Chemopreventative Agent in the
Potential Treatment of Cardiovascular Diseases
Jingjing Yu, Michel Weiwer, Robert J. Linhardt
and Jonathan S. Dordick
Oxidative stress has been linked to the origin and progression
of cardiovascular diseases. Nicotinamide adenine dinucleotide
phosphate, reduced form (NADPH) oxidase is a multi-component,
NADPH-dependent enzyme that generates superoxide anion in
the presence of molecular oxygen. The enzyme has been identified
and characterized in all 3 vascular wall cell types and represents
the major source of reactive oxygen species (ROS) production
in the vascular wall. Inhibition of NADPH oxidase activation
appears to suppress the sequence of cellular events that leads
to a variety of cardiovascular diseases, including atherosclerosis.
The naturally occurring methoxyphenol apocynin has been found
to inhibit NADPH oxidase upon activation by peroxidases (e.g.
soybean peroxidase, myeloperoxidase) or ROS under mild reaction
conditions. Upon peroxidase-catalyzed activation, the apocynin
oxidation products act to block the assembly and activation
of NADPH oxidase. Although the mechanism of inhibition of
NADPH oxidase remains largely unknown, apocynin’s high
effectiveness and low toxicity makes it a promising lead compound
in the development of new therapeutic agents for cardiovascular
diseases.
[Back to top]
Impact of Traditional Therapies and Biologics
on Cardiovascular Diseases in Rheumatoid Arthritis
Jean-Frédéric Boyer, Alain
Cantagrel and Arnaud Constantin
In chronic inflammatory diseases such as rheumatoid arthritis
(RA), systemic inflammation appears as an independent risk
factor, contributing to increased cardiovascular mortality.
This high cardiovascular mortality reveals the existence of
accelerated atherosclerosis, the pathogenesis of which may
be associated with traditional risk factors such as smoking,
hypertension, dyslipidemia, deterioration of insulin sensitivity,
and less traditional risk factors such as hyperhomocysteinemia,
inflammatory conditions and endothelial dysfunction. Control
of systemic inflammation theoretically provides a means of
preventing this higher cardiovascular mortality among RA patients.
In this review we address the question of the impact of anti-rheumatic
drugs currently used in RA, such as non-steroidal anti-inflammatory
drugs (e.g. non-selective or cyclooxygenase-2 selective inhibitors),
steroidal anti-inflammatory drugs (glucocorticoids), traditional
disease-modifying anti-rheumatic drugs (e.g. methotrexate)
or biologics (e.g. anti-tumour necrosis factor alpha anti-tumour
necrosis factor alpha) on cardiovascular diseases in RA patients.
We also discuss the specific mechanisms involved in the differential
cardiovascular effects of these therapeutic agents.
[Back to top]
Amiodarone Hepatotoxicity
Mohamed Babatin, Samuel S. Lee and P.
Timothy Pollak
Potential hepatotoxicity related to amiodarone therapy
is often a concern when deciding whether to initiate or continue
treatment with this medication. While mostly associated with
long-term oral administration of the drug, toxicity has also
been reported early during intravenous administration and
months after discontinuation of therapy. In the majority of
patients, it is discovered incidentally during routine testing
of liver biochemistry and rarely do the hepatic effects develop
into symptomatic liver injury or failure. Despite the widespread
use of amiodarone, prospective clinical studies have been
sparse and there has been little consensus among experts in
the field regarding optimum monitoring for adverse effects
in patients receiving this drug. In order to examine the current
state of knowledge surrounding the incidence, pathogenesis
and mechanism of liver effects associated with amiodarone,
the existing literature was reviewed, with particular emphasis
on clinical recommendations for monitoring.
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