Vascular Disease Prevention (Discontinued) - Volume 1, Issue 3, 2004

The heart is a major site of natriuretic peptides (NP). Atrial and brain natriuretic peptide (ANP and BNP) are predominantly produced by atria and ventricles. C-Natriuretic peptide (CNP) is also found in heart tissue. ANP and BNP are produced by cardiomyocytes and fibroblasts. Cardiac fibroblasts also secrete CNP. Three NP-receptors (NPR-A, NPRB, NPR-C) are expressed in heart atria and ventricles. ANP, BNP and CNP exert antihypertrophic actions in cardiomyocytes, suppress cardiac fibroblast growth and inhibit collagen synthesis in cardiac fibroblasts. In vivo infusion of ANP also reduces collagen deposition in the arterial wall of spontaneously hypertensive rats. Baseline plasma BNP is a sensitive predictor of morbidity and mortality in heart failure and changes in BNP over time are associated with corresponding changes in subsequent mortality and morbidity. Plasma BNP, and to a lesser extent ANP, is also a strong cardiovascular risk marker in patients with essential hypertension and left ventricular hypertrophy without left ventricle dysfunction or overt renal disease. A potential role for genetic variants of the ANP gene in the modulation of the disease phenotype observed with some cardiovascular diseases is also reported. Neutral endopeptidase inhibition may also have inhibitory effects on cardiac hypertrophy and fibrosis.

Selectins are important leukocyte adhesion molecules mediating the initial capture and rolling of leukocytes and therefore contributing to an effective recruitment of leukocytes to sites of inflammation. In animal models, blockade of P-, E-, or L-selectin-dependent leukocyte rolling has been shown to protect from several acute and chronic inflammatory diseases such as ischemia / reperfusion injury, asthma, psoriasis, and atherosclerosis. While selectins often act in an overlapping fashion novel pan-selectin antagonists have been developed with promising results in experimental studies. This led to the initiation of first clinical trials in patients with asthma and psoriasis. Interestingly, clinical trials aiming at blocking selectins in acute inflammatory diseases are still lacking, but patients suffering from stroke, myocardial infarction, or renal ischemia might benefit from a selectin blocking therapy if started early after onset of ischemia. In conclusion, blocking selectin function may have a role in disease prevention for both acute and chronic inflammatory diseases. But, since selectins in humans functionally differ from selectins in other species, results from studies in nonhuman species should be carefully translated into clinical trials.

Oxygen occupies a key role in cellular metabolism and function. Oxygen delivery to cells is crucial and a lack of oxygen such as occurs during myocardial infarction can be lethal. Cells must therefore be able to respond to changes in oxygen tension. Since the first studies examining the acute cellular effect of hypoxia on activation of transmitter release from glomus or type I chemoreceptor cells, it is now known that virtually all cells are able to respond to changes in oxygen tension. Despite advances made in characterising hypoxic responses, the identity of the oxygen sensor remains debated. Recently, more evidence has evolved as to how cardiac myocytes sense acute changes in oxygen. This review will examine the available evidence in support of acute oxygen sensing mechanisms with special reference to the heart. Further understanding these cellular processes should lead to interventions that assist in preventing the deleterious effects of acute changes in oxygen tension such as alterations in contractile function and cardiac arrhythmia.

Degenerative, nonrheumatic aortic valve stenosis is the most common acquired valve disease. Regardless whether the stenosis develops on a congenitally normal or abnormal (bicuspid) aortic valve, the progressive fibrosis, calcification, fusion and degeneration of the aortic cusps can be regarded as an atherosclerotic disease. Accordingly, it is strongly correlated to the prevalence of coronary artery disease. Stenotic valves show histologic characteristics similar to atherosclerotic lesions and induce a systemic subclinical inflammatory response. Severe symptomatic aortic stenosis is an indication for surgical valve replacement. There is, however, no established medical treatment to delay the progression of aortic valve stenosis in asymptomatic patients. Recent retrospective studies suppose that statin treatment inhibits the accumulation of aortic valve calcification, as assessed by electron beam computed tomography (EBCT), or delay progression of elevated hemodynamic parameters such as systolic pressure gradients or peak aortic jet velocity, as measured by Doppler echocardiography. Mechanisms responsible for the potential benefit of statins for patients with aortic valve stenosis may be mediated by pleiotropic effects besides lipid lowering. These may include anti-inflammation, anti-angiogenesis, inhibition of matrix degrading enzymes, as well as modulation of local lipid oxidation and / or immune responses. Ongoing randomized prospective clinical trials will provide much stronger evidence for or against the recommendation of aggressive treatment with statins to slow the process of aortic valve stenosis.

Peripheral arterial disease (PAD) has an increasing prevalence and incidence; 30% of the patients with intermittent claudication die within 5 years. Therapeutic goals are therefore a reduction of the high cardiovascular mortality and improvement of the ischaemic symptoms. The review describes the medical treatment options for the different stages of PAD and focuses on new treatment strategies, like the local application of growth factors or autologous stem cells.

The most common symptom of patients with peripheral arterial disease [PAD] is intermittent claudication. Symptomatic peripheral vascular disease carries at least a 30% risk of death within five years and almost 50% within 10 years, primarily due to myocardial infarction [60%] or stroke [12%]. Lifestyle modification should be an integral component of secondary preventive therapy and complete cessation of tobacco use and regular exercise should be recommended for all patients. Lifestyle changes are also important in addressing / modifying the risk factors for PAD. Intensive pharmacological risk factor modification is another important part of the management of PAD.

Inhibition of exogenous thrombin is impaired in neonatal compared to normal adult plasma due to neonatal antithrombin (AT) deficiency. It has been suggested that newborn infants may be resistant to antithrombotic therapy [administration of unfractionated heparin (UH), low molecular weight heparin (LMWH), antithrombin-heparin complex (ATH)] during overt thrombotic disease when the neutralisation of abnormal thrombin activity is the therapeutic goal. The effects of anticoagulant drugs on de-novo thrombin generation in both cord and adult plasma are influenced by the type of plasma activation applied. In the presence of high amounts of initiator, as usual in conventional clotting assays, cord plasma is significantly more susceptible to addition of the anticoagulant drugs UH, LMWH, ATH, and recombinant human activated protein C (rhAPC) than adult plasma due to reduced neonatal thrombin potential. It can be speculated that lower doses of these anticoagulant drugs may be required to prevent de-novo thrombin generation and possibly thrombosis in newborn infants than in older patients. In contrast, in the presence of low amounts of lipidated tissue factor (TF) to trigger clot formation, probably simulating in-vivo conditions more closely than strong activation, cord plasma is significantly less susceptible to addition of rhAPC and possibly of other anticoagulant drugs. It has been shown that the low anticoagulant efficacy of rhAPC is attributable to the low neonatal levels of tissue factor pathway inhibitor (TFPI) and AT, resulting in concomitant low anticoagulant action of TFPI, AT, and rhAPC associated with efficient thrombin generation in neonates. From this point of view, higher doses of anticoagulant drugs may be required to prevent de-novo thrombin generation and possibly thrombosis in newborn infants than in older patients.

Sesamin is one of the lignans found in high concentration in sesame seeds and oil. Several studies have demonstrated the protective effects of sesamin against the liver injury, which is mainly due to its antioxidative activity. However, little is known about the biological activities of sesamin in cardiovascular system. We have recently obtained evidence that dietary sesamin efficiently suppressed the development and maintenance of hypertension in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive, two-kidney, one-clip renal hypertensive, and salt-loaded stroke-prone spontaneously hypertensive rats. The suppressive effect of sesamin on blood pressure elevation was closely related to an inhibitory effect on excessive superoxide (O2 -) production in the aorta of hypertensive animals. In addition, dietary sesamin normalized the decrease in endothelium-dependent vasodilatory responses and the increase in α1- adrenoceptor-dependent vasoconstrictor responses in DOCA-salt hypertensive model. We propose that the dietary sesamin is useful as a prophylactic treatment in the development of hypertension and endothelial dysfunction, and suggest that the antioxidative property of sesamin may apply to the prevention of oxidative stress-related diseases, such as diabetes, hypercholesterolemia, and atherosclerosis.

Cardiovascular diseases (CVD) are the major causes of morbidity and mortality in Western communities. Moreover, type 2 diabetes mellitus (DM) has become one of the most frequent diseases challenging physicians and its prevalence is rapidly increasing. The metabolic syndrome is associated with an increased risk of cardiovascular disease and type 2 DM. The most common manifestations of the metabolic syndrome are insulin resistance, central obesity, hypertension and dyslipidemia. Other components often associated with the metabolic syndrome are endothelial dysfunction, a proinflammatory and prothrombotic state, microalbuminuria, hyperuricemia, non-alcoholic fatty liver disease (NAFLD) and hyperhomocysteinemia. The underlying mechanism that can explain most -if not all- of the disturbances of the metabolic syndrome is insulin resistance. The primary goal of treating metabolic syndrome is the prevention of type 2 DM and cardiovascular events. Non-pharmacological means (life-style changes and weight reduction) should be the first line therapy in patients with the metabolic syndrome, accompanied by drugs when necessary. This review summarises the new insight aspects of metabolic syndrome and focuses on how to prevent and treat cardiovascular complications in patients with the metabolic syndrome.

Prostacyclin (PGI2) inhibits platelet aggregation, and vasoconstriction. Prostacyclin synthase (PGIS), a catalyst of PGI2 formation from prostaglandin H2, is widely distributed and predominantly found in vascular endothelial and smooth muscle cells. The PGIS gene is localized to 20q13.11-13 and thought to be a candidate gene for cardiovascular disease. Several mutations and polymorphisms in the gene were reported to be associated with cardiovascular diseases. These results suggest that PGI2 function depends on the different alleles of the PGIS gene and may influence the risk of cardiovascular diseases. Thus, tailor-made management, such as the administration of PGI2 analogs, may be selected on the basis of individual variants of this gene for prevention of cardiovascular diseases.

The aim of this study was to determine whether ultrasound features of polycystic ovaries (PCO) are associated with Metabolic Syndrome (MetS), a condition linked with an increased risk of vascular events. A total of 66 women had ultrasound scans of their ovaries. There was no significant difference in the prevalence of MetS among women with unilateral or bilateral ultrasound evidence of PCO compared with women with no ultrasound evidence of PCO. The finding of PCO alone on ultrasound may be of no metabolic significance and a poor screening tool for cardiovascular risk. Resources should be shifted from the current emphasis on ultrasound diagnosis of PCO Syndrome to improved endocrine and metabolic characterisation and treatment. This approach may, in turn, identify those women at highest risk of vascular events.