Current Pharmaceutical Design - Volume 22, Issue 1, 2016

The response to the harm caused by risk factors related to atherosclerosis may consist of clinical-signs of cardiac and/or blood vessel ischemic pathology sometimes accompanied by arrhythmias and heart failure-, metabolic- signs of altered oxygen transport and pro-thrombotic changes of coagulation-fibrinolysis cascade-, and sympathetic features due to nerve stimulation, which cause changes in heart rate and blood pressure. Moreover, some special categories like women have the responses, which are influenced by their endocrine constellation. There is a different predisposition towards the markers of atherosclerosis in premenopausal woman, who displays atherogenic effects, and in women after the menopause who respond similarly to that of men. Finally, oxidative stress, which is a strong pro-thrombotic factor, increases the development of an atherosclerotic lesion. From these data, there is no doubt that a large number of factors, primarily smoking and endothelial dysfunction influence the cardiovascular system causing a major incidence of cardiovascular events. In addition, there would be evidence that some factors related to atherosclerosis should be considered as an etiologic (causal) factor of cardiovascular alterations because they can lead, in the long run, to an irreversible damage to the heart and blood vessels.

Statins exert beneficial effects on cardiovascular [CV] outcomes as well as on inflammation and oxidative stress. The widespread use of statins for both primary and secondary CV disease prevention is based on the evidence from large randomized controlled trials. The benefits of statin treatment outweigh any harm in high risk patients. In this narrative review, we provide an update on several aspects of statin treatment based on the most recent evidence in this field.

Both high arterial blood pressure (BP) and elevated levels of fine particulate matter (PM2.5) air pollution have been associated with an increased risk for several cardiovascular (CV) diseases, including stroke, heart failure, and myocardial infarction. Given that PM2.5 and high BP are each independently leading risk factors for premature mortality worldwide, a potential relationship between these factors would have tremendous public health repercussions. Therefore, the aim of this review is to summarize recent evidence linking air pollution and BP. Epidemiological findings demonstrate that particulate pollutants cause significant increases in BP parameters in relation to both short and long-term exposures, with robust evidence for exposures to PM2.5. Moreover, recent epidemiological studies suggest a positive association between residence within regions with higher levels of ambient PM and an increased incidence and prevalence of overt hypertension. Studies provide consistent results that elevated concentrations of pollutants increase hospital admissions and/or emergency visits for hypertensive disorders and also support that PM levels increases BP in vulnerable subsets of individuals (pregnant women, high CV risk individuals). In this context, PM-mediated BP elevations may be an important pathway which acts as a potential triggering factor for acute CV events. Mechanistic evidence illustrates plausible pathways by which acute and chronic exposures to air pollutants might disrupt hemodynamic balance favoring vasoconstriction, including autonomic imbalance and augmented release of various pro-oxidative, inflammatory and/or hemodynamically-active mediators. Together these responses may underlie PM-induced BP elevations; however, full details regarding the responsible mechanisms require further studies. As a consequence of the ubiquity of air pollution, even a small effect on raising BP and/or the prevalence of hypertension, i.e. the major risk factor for mortality and morbidity worldwide, would have enormous global public health implications.

Ghrelin is a growth hormone-releasing peptide, isolated from the stomach. Researches in progress documented that ghrelin participates in the stimulation of the hypothalamus-pituitary-adrenal axis at the hypothalamic level and in the regulation of energy balance. Growth hormone-independent functions have been ascribed to ghrelin. Among others, a large body of literature demonstrated the presence of specific receptors for ghrelin, distributed at the level of cardiomyocytes and endothelial cells. Therefore, a link between ghrelin and cardiovascular system has been hypothesized and, then, demonstrated in both experimental and clinical studies. Ghrelin has largely documented cardiac beneficial effects, including protection from ischemia/reperfusion injury, attenuation of left ventricular remodeling following myocardial infarction, and improvement of left ventricular function. Exercise level in patients with chronic heart failure had also been seen. Ghrelin exerts these effects through several mechanisms, including the inhibition of apoptosis. At the level of blood vessels, ghrelin exerts a significant impact on vascular function. In particular, acutely infused, ghrelin reverses endothelial dysfunction by increasing NO availability and restores the endothelin-1/nitric oxide imbalance in the peripheral microcirculation of patients with metabolic syndrome. Antioxidant/anti-inflammatory effects, and-or an ameliorated insulin sensitivity are proposed mechanisms whereby ghrelin exerts its vascular protective actions. At higher doses, ghrelin also decreases blood pressure, by mechanisms that involve the modulation of sympathetic nervous system. This finding highlights the ghrelin system as a promising candidate for cardiovascular drug discovery.

Alterations in myocardial metabolism and blood flow have been described in patients with metabolic disorders, cardiovascular disease and cardiomyopathies, and have been implicated in the pathogenesis or prognosis of cardiac conditions. Adipose tissue dysfunction occurs in the above categories of patients. Adipose tissue plays a fundamental role in the modulation and selection of nutrients reaching the myocardium, and adipocytes secrete adipokines and other molecules affecting myocardial metabolism and regulating vascular function. In turn, the myocardium secretes a series of peptides affecting adipose tissue metabolism, and adipose tissue vascularization and perfusion contribute to the maintenance of adipose tissue health. This review addresses the reciprocal interaction linking adipose tissue to myocardial metabolism and vascular function. We summarize evidence of factors released by adipose tissue that affect cardiac metabolism and vice versa. Then, we address the role of adipose tissue in regulating vascular health, and examine whether adipose tissue hypoperfusion is causative or defensive of adipose tissue dysfunction.

Obesity, a chronic low-grade inflammation disorder characterized by an expansion in adipose tissue mass, is rapidly expanding worldwide leading to an increase in the incidence of comorbidities such as insulin resistance, type 2 diabetes and cardiovascular diseases. This has led to a renewed interest in the adipose tissue function, historically considered as a passive fat storage. It is now well established that adipose tissue is an organ with an active role in production and release of a variety of molecules called adipocytokines. Dysregulated production of adipocytokines seems to be responsible for the pathogenesis of insulin resistance and type 2 diabetes; however, the mechanisms are still unclear. Hypoxia, that occurs when adipocytes expand in obesity, has been proposed as a possible cause of adipose tissue inflammation. On the other hand, recent studies have shown that adipose tissue oxygen tension was actually higher (hyperoxia) than normal and associated with insulin resistance in obesity, despite a reduction in blood flow. This might be explained by the role of mitochondrial oxygen consumption. Hence, further studies are needed to understand the role of adipose tissue oxygenation and perfusion in obesity to assess pathophysiology and novel opportunities for treating the diseases.

Most recent technical innovations in cardiovascular MR imaging (CMRI) are presented in this review. They include hardware and software developments, and novelties in parametric mapping. All these recent improvements lead to high spatial and temporal resolution and quantitative information on the heart structure and function. They make it achievable ambitious goals in the field of magnetic resonance, such as the early detection of cardiovascular pathologies. In this review article, we present recent innovations in CMRI, emphasizing the progresses performed and the solutions proposed to some yet opened technical problems.

Magnetic resonance angiography (MRA) is a non-invasive technology that can be used for diagnosis and monitoring of cardiovascular disease; the number one cause of mortality worldwide. Hyperpolarized imaging agents provide signal enhancement of more than 10, 000 times, which implies large reduction in acquisition time and improved spatial resolution. We review the role of hyperpolarized 13C agents for MR angiography and present the literature in the field. Furthermore, we present a study of the benefit of intra-arterial injection over intravenous injection of hyperpolarized agent for cerebral angiography in the rat, and compare the performance of two standard angiographic pulse sequences, the gradient echo (GRE) sequence and the balanced steady-state free precession (bSSFP). 2D coronal cerebral angiographies using intra-arterial injections were acquired with a GRE sequence with in-plane resolution of 0.27 mm and matrix size 256x128, and 2D coronal cerebral angiographies were acquired with a bSSFP sequence with in-plane resolution of 0.55 mm and matrix size 128x64. The bSSFP sequence provides higher SNR in phantoms than the GRE sequence. Similarly, intravenous injections are imaged with higher SNR with the bSSFP sequence, where the signal destruction of the GRE sequence is avoided. However, for intra-arterial injections, the bSSFP sequence results in strong artefacts, and the GRE sequence is preferred. Hyperpolarized MRA presents many challenges and cannot currently compete with conventional contrast enhanced MRA. Further research may change this since hyperpolarization is still an immature methodology.

Hybrid imaging devices including PET/CT and SPECT/CT have seen a great success since these scanners found their way into clinical routine – although this success is mainly based on the use in oncological imaging. But also the advent of PET/MRI holds great promise. The combined assessment of molecular imaging and morphology making use of the variety of PET tracers and the high spatial resolution from CT or MRI has the potential of an increased diagnostic accuracy all imaging but especially in cardiovascular questions. We put special emphasis on PET/MR although the experience is still limited. However, as the use of MR imaging in the assessment of myocardial viability as a prime example where assessing myocardial metabolism – even if done so indirectly - is so widespread in clinical reality, this appears to be justified. Thus, in this review, we aim to outline technical characteristics of hybrid imaging systems and highlight their use in cardiovascular diseases and their applications.

When designing clinical trials for testing novel cardiovascular therapies, it is highly relevant to understand what a given technology can provide in terms of information on the physiologic status of the heart and vessels. Ultrasound imaging has traditionally been the modality of choice to study the cardiovascular system as it has an excellent temporal resolution; it operates in real-time; it is very widespread and - not unimportant - it is cheap. Although this modality is mostly known clinically as a two-dimensional technology, it has recently matured into a true three-dimensional imaging technique. In this review paper, an overview is given of the available ultrasound technology for cardiac chamber quantification in terms of volume and function and evidence is given why these parameters are of value when testing the effect of new cardiovascular therapies.

Vascular aging represents a progressive procedure involving biochemical, enzymatic, and cellular changes of the vascular tree. Early vascular aging (EVA), is defined as the inappropriate for age of vascular damage. Increased for age arterial stiffness is a biomarker that should be considered as a cardiovascular (CV) risk factor that can be manipulated. EVA is a new tool for guidance in everyday clinical praxis for patients at increased CV risk or a positive family history of early onset of cardiovascular events, such as stroke or coronary artery disease. Understanding the mechanisms promoting or protecting from EVA, a process that is in close relationship with CV diseases. The role of hypertension treatment against the development of vascular damage is important and different strategies could have a considerable impact on future vascular health.