Cardiovascular
& Hematological Disorders - Drug Targets
ISSN: 1871-529X
Current Drug Targets - Cardiovascular
& Hematological Disorders
Volume 7, Number 1, March 2007
Contents
Medial Vascular Calcification in Diabetes Mellitus
and Chronic Kidney Disease: The Role of Inflammation
Pp. 1-6
Ziyad Al-Aly
[Abstract] [Full
Text Article]
Statins in the Prevention of Cardiovascular Events
in Patients with Renal Failure Pp. 7-13
Michele Buemi, Fulvio Floccari, Lorena Nostro, Susanna
Campo, Chiara Caccamo, Alessio Sturiale, Carmela Aloisi, Maria
Stella Giacobbe and Nicola Frisina
[Abstract] [Full
Text Article]
The Role of Coronary Angioplasty in the Management
of Patients with Stable Coronary Artery Disease Pp.
15-20
Demosthenes G. Katritsis
[Abstract] [Full
Text Article]
Potential Therapeutic Targets in Cirrhotic Cardiomyopathy
Pp. 21-26
Massimo Pozzi, Laura Ratti, Cristina Guidi, Maria Milanese
and Giuseppe Mancia
[Abstract] [Full
Text Article]
The Role of Catecholamines in Formation and Resolution
of Pulmonary Oedema Pp. 27-35
Beate Rassler
[Abstract] [Full
Text Article]
Neural Control of Blood Pressure: Focusing on Capsaicin-Sensitive
Sensory Nerves Pp. 37-46
Youping Wang and Donna H. Wang
[Abstract] [Full
Text Article]
Discovery of New Cardiovascular Hormones for the Treatment
of Congestive Heart Failure Pp. 47-62
David L. Vesely
[Abstract] [Full
Text Article]
Orthostatic Hypotension: Evaluation and Treatment
Pp. 63-70
Simona Maule, Grazia Papotti, Diego Naso, Corrado Magnino,
Elisa Testa and Franco Veglio
[Abstract] [Full
Text Article]
Peptides Derived from Platelet Non-integrin Collagen-receptors
or Types I and III Collagen Inhibit Collagen-Platelet Interaction
Pp. 71-75
Thomas M. Chiang, J. Zhu and Virginia Woo-Rasberry
[Abstract] [Full
Text Article]
Abstracts
[Back to top]
Medial Vascular Calcification in Diabetes Mellitus and Chronic
Kidney Disease: The Role of Inflammation
Ziyad Al-Aly
[Full
Text Article]
Medial vascular calcification in an increasingly recognized
problem in patients with diabetes and patients with chronic
kidney disease. Calcification of the media is associated with
significant morbidity and mortality. The phenotypic and the
molecular fingerprints of medial calcification in patients
with diabetes and patients with chronic kidney disease are
strikingly similar. While disturbances in divalent ion homeostasis
have been proposed to play a role in calcification of the
media in patients with chronic kidney disease, patients with
diabetes have an apparently intact bone and mineral metabolism.
Chronic kidney disease as well as diabetes are now recognized
as pro-inflammatory states. This review will explore the pathobiology
of medial vascular calcification, review the evidence for
diabetes and chronic kidney disease as pro-inflammatory states,
and discuss the role of inflammation as a mechanistic link
that explains the similarities in phenotypic and molecular
characteristics of medial calcification in patients with chronic
kidney disease and patients with diabetes mellitus.
[Back to top]
Statins in the Prevention of Cardiovascular Events
in Patients with Renal Failure
Michele Buemi, Fulvio Floccari, Lorena Nostro, Susanna
Campo, Chiara Caccamo, Alessio Sturiale, Carmela Aloisi, Maria
Stella Giacobbe and Nicola Frisina
[Full
Text Article]
HMG-CoA reductase inhibitors (statins) are among the most
widely used hypolypemizing drugs with a pleiotropic activity.
Numerous clinical trials have demonstrated that statins can
have a significant effect in the prevention of cardiovascular
diseases in the general population. In patients with renal
failure, this drug preserves the hypolypemizing efficacy found
in the general population without increasing their unwanted
side-effects.
The re-analysis of data from epidemiological studies conducted
on the general population has confirmed that statins provide
cardiovascular protection also in subjects with renal failure.
These data have been partly confirmed by the findings made
by 4D (Die Deutsche Diabetes Dialyse Studie) and Alert studies,
conducted on diabetic patients on dialysis and patients with
renal transplants, respectively.
The results of other studies, such as AURORA, SHARP, REnal
and Vascular End stage Disease, and ESPLANADE, clearly indicate
that statins prevent cardiovascular disease in patients with
renal insufficiency, just as they do in the general population.
[Back to top]
The Role of Coronary Angioplasty in the Management
of Patients with Stable Coronary Artery Disease
Demosthenes G. Katritsis
[Full
Text Article]
A review of the existing evidence on the impact of percutaneous
coronary intervention (PCI) in the setting of stable coronary
artery disease (CAD) indicates that in patients with chronic
coronary artery disease and good left ventricular function,
PCI does not confer any clear benefit in terms of hard long-term
clinical outcomes, such as mortality, myocardial infarction
or the need for subsequent revascularization, as compared
with medical conservative treatment. By comparing the benefits
against cost considerations, it seems that many percutaneous
interventions that are currently performed in patients with
non-acute CAD are probably not justified.
Determination of the functional significance of coronary artery
disease can often be a challenge. Conventional coronary angiography
and imaging tests, although suitable for risk stratification,
may not be satisfactory as independent guides for specific
decision-making regarding the optimum management of these
patients.
The development of more efficient methods for the identification
of coronary lesions that should be the target of coronary
intervention is certainly needed.
[Back to top]
Potential Therapeutic Targets in Cirrhotic Cardiomyopathy
Massimo Pozzi, Laura Ratti, Cristina Guidi, Maria Milanese
and Giuseppe Mancia
[Full
Text Article]
Cirrhotic cardiomyopathy is a recently identified pathological
condition defined as "a chronic cardiac dysfunction in
patients with cirrhosis characterized by blunted contractile
responsiveness to stress and/or altered diastolic relaxation
with electrophysiological abnormalities, in the absence of
known cardiac disease". Overall there seems to be a link
between the progression of liver function impairment, the
development of portal hypertension and the degree of hyperdynamic
circulation, the hallmark of the deranged cardiovascular function
in advanced liver diseases. Although mechanical factors contribute
to much of the increased resistance within the liver in portal
hypertension, there is clearly a vasculogenic component to
the development, perpetuation and progression of this syndrome
as well. The vascular component of portal hypertension includes
an increase in splanchnic blood flow, as well as an increase
in intrahepatic vascular resistance. Dysregulation of the
nitric oxide system appears to play a key role in both these
processes with a paradoxical reduction of intrahepatic availability
despite increased disposal in the splanchnic and other vascular
districts with adverse effects on cardiac function and structure.
Nevertheless, other putative mediators of cardiac damage in
cirrhosis have been proposed and their role in the pathogenesis
of cirrhotic cardiomyopathy investigated.
This review involves a discussion of data achieved on pathogenesis
and clinical features of cirrhotic cardiomyopathy but mainly
focuses on considerations on potential therapeutic targets,
in the light of the evidence that this mainly subclinical
condition merges to clinical relevance when challenged with
those therapeutic interventions and procedures currently employed
to treat the major complications of cirrhosis that might produce
a negative impact on the cardiovascular system.
[Back to top]
The Role of Catecholamines in Formation and Resolution
of Pulmonary Oedema
Beate Rassler
[Full
Text Article]
Pulmonary oedema (PO) can emerge from mechanical disorders
in pulmonary circulation leading to elevated fluid filtration
in the lung, or from increased vascular permeability due to
inflammatory or toxic injury of the alveolar-capillary barrier.
A number of these disorders causing PO is associated with
increased catecholamine (CA) levels in plasma and lung tissue
and/or increased sympathetic activation such as neurogenic
PO, high-altitude PO or PO in patients with phaeochromocytoma.
Experimental CA stimulation in animals induced PO after less
than one hour of infusion. Both α-
and β-adrenergic
mechanisms are involved in the pathogenesis but also in the
resolution of PO. CAs increase pulmonary capillary pressure
and thus, enhance fluid filtration into the pulmonary interstitium.
Additionally, by activation of proinflammatory cytokines,
they induce pulmonary inflammation that may lead to capillary
leak. Finally, they play an important role in the regulation
of alveolar fluid clearance. The present paper considers the
pathways by which CAs contribute to the development of PO
of various origin.
[Back to top]
Neural Control of Blood Pressure: Focusing on Capsaicin-Sensitive
Sensory Nerves
Youping Wang and Donna H. Wang
[Full
Text Article]
Hypertension is a major risk factor leading to devastating
cardiovascular events such as myocardial infarction, stroke,
heart failure, and renal failure. Despite intensive research
in this area, mechanisms underlying essential hypertension
remain to be defined. Accumulating evidence indicates that
neural components including both sympathetic and sensory nerves
innervating the cardiovascular and renal tissues play a key
role in regulating water and sodium homeostasis and blood
pressure, and that abnormalities in these nervous systems
contribute to increased salt sensitivity and development of
hypertension. In contrast to relatively well-defined sympathetic
nervous system, the role of sensory nerves in the control
of cardiovascular homeostasis is largely unknown. Data from
our laboratory show that degeneration of capsaicin-sensitive
sensory nerves renders a rat salt sensitive in terms of blood
pressure regulation. Evidence is also available indicating
that sensory nerves, in interacting with other neurohormonal
systems including the sympathetic nervous system, the renin-angiotensin
aldosterone system, the endothelin system, and superoxide,
regulate cardiovascular and renal function in such that they
play a counter-balancing role in preventing salt-induced increases
in blood pressure under pathophysiological conditions. Altered
activity of the sensory nervous system, a condition existed
in both genetic and experimental models of hypertension, contributes
to the development of hypertension. This article focuses on
reviewing the current knowledge regarding the possible role
of sensory nerves in regulating blood pressure homeostasis
as well as the function and regulation of novel molecules
expressed in sensory nerves.
[Back to top]
Discovery of New Cardiovascular Hormones for the Treatment
of Congestive Heart Failure
David L. Vesely
[Full
Text Article]
In 1628, Harvey first correctly described the heart as a pump.
It was another 350 years before the heart was established
as an endocrine gland that synthesized a family of peptide
hormones that regulate blood volume and blood pressure. There
are now five peptide hormones made in the heart which have
been demonstrated to have beneficial effects in persons with
congestive heart failure. One of these peptide hormones i.e.
brain natriuretic peptide (BNP) is commercially available
and has been widely used in the United States for the treatment
of acute congestive heart failure under the name Nesiritide/Natrecor®.
Nesiritide has one serious side effect, i.e. it may worsen
renal function in persons with acute decompensated cardiac
failure. The best of these peptide hormones for the treatment
of chronic heart failure is a cardiac hormone named vessel
dilator which enhances sodium and water excretion 4- to 5-fold
in persons with congestive heart failure but vessel dilator’s
biologic effects lasts six hours compared to less than 30
minutes for BNP, without the deleterious effects of BNP on
renal function. This review will focus on six cardiac hormones’
discovery, identification and comparison of their beneficial
effects and side effects in humans with congestive heart failure.
[Back to top]
Orthostatic Hypotension: Evaluation and Treatment
Simona Maule, Grazia Papotti, Diego Naso, Corrado Magnino,
Elisa Testa and Franco Veglio
[Full
Text Article]
Orthostatic hypotension (OH) may be dependent upon various
neurogenic and non-neurogenic disorders and conditions. Neurogenic
causes include the main autonomic failure syndromes, primary
(multiple system atrophy, pure autonomic failure, and autonomic
failure associated with Parkinson’s disease) and secondary
(central nervous system diseases, peripheral neuropathies
and systemic diseases). Non-neurogenic causes of OH include
cardiac impairment, fluid and electrolyte loss, vasodilatation,
and old age. A number of drugs may also cause OH, through
their vasoactive action or by interfering with the autonomic
nervous system.
Symptoms of OH are debilitating, often confining patients
to bed, and longitudinal studies have shown that OH increases
the risk of stroke, myocardial ischemia and mortality.
The therapeutic goal is to decrease the incidence and severity
of postural symptoms, rather than restore normotension. In
non-neurogenic OH, treatment of the underlying cause may be
curative. In neurogenic OH a combination of non-pharmacological
and pharmacological measures is often needed. Patient education
and non-pharmacological measures represent the first step;
among these interventions, fluid repletion and physical countermanoeuvres
have been proven very effective. Pharmacological treatment
comprises a number of agents acting on blood vessels, on blood
volume or with other pressor mechanisms. The drugs most currently
used are fludrocortisone and midodrine. Fludrocortisone expands
the extravascular body fluid volume and improves α-adrenergic
sensitivity. Midodrine is a peripheral, selective α1-adrenergic
agonist that causes arterial and venous vasoconstriction.
Despite the wide use of these drugs, multicentre, randomised
and controlled studies for the treatment of OH are still scarce
and limited to few agents and groups of patients. Pharmacological
management of OH substantially improves the quality of life
of patients, although it may be problematic. The development
of supine hypertension and subsequent congestive heart failure
should be avoided, especially in those patients with a pre-existing
cardiovascular risk, such as in diabetes or ischemic heart
disease.
[Back to top]
Peptides Derived from Platelet Non-integrin Collagen-receptors
or Types I and III Collagen Inhibit Collagen-Platelet Interaction
Thomas M. Chiang, J. Zhu and Virginia Woo-Rasberry
[Full
Text Article]
Platelet-collagen interaction plays an important
role in hemostasis and pathological thrombosis. Upon an injury
to the subendothelium of a blood vessel wall, platelets adhere
to the denuded substrate, aggregate, and release biological
substances. Many investigators have explored the use of blocking
agents to interrupt the final step of binding fibrinogen on
glycoprotein (GP) IIb/IIIa of activated platelets. A potent
peptide is Arg-Gly-Asp-Ser (RGDS) and its derivatives in various
forms. Results from many clinical trials show that the efficacy
of these antagonists does not lie in blocking the adhesion
of platelets to the distal site(s) of the injury as expected.
Because type I and type III collagens are predominant components
of blood vessel walls, other laboratories and ours have defined
various active peptides from either collagen molecules or
platelets as useful for blocking collagen-platelet interaction.
An active hybrid peptide derived from both platelet types
I and type III collagen receptors that abolishes type I and
type III collagen-induced platelet aggregation has been obtained.
The hybrid peptide inhibits the binding of type I and type
III collagens to washed human platelets, platelet aggregation,
and the adhesion of washed platelets to rabbit aortic segments.
However, the usefulness of the defined hybrid peptide in preventing
thrombi formation in vivo requires further investigation.
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