Current Pharmaceutical Design - Volume 20, Issue 9, 2014

The key oxygen sensing molecules, Prolyl-hydroxylase domain 1-3 enzymes (PHD1-3), regulate hypoxia-inducible factor (HIF) under hypoxia. In the settings of cardiomyopathy and ischemia-reperfusion injury, PHD3 expression is elevated, resulting in decreased HIF activation. The role of PHD3 in myocardial injury is poorly understood. Hence, we aimed to determine the effects of PHD3 deletion in mice on HIF-1α and other related Read More

Inflammation reduces pharmacological response to β1-blockers by down-regulating the target receptor protein. This may contribute to the sub-optimal response to pharmacotherapy with β-blockers. Nebivolol is a third generation β-adrenoceptor (AR) blocker with high selectivity for blocking β1 and β3-agonistitic properties. We studied whether response to nebivolol is also reduced by inflammation. Male Sprague-Dawley rats ( Read More

Although recent studies have underscored the role of the heme-oxygenase (HO) inducer hemin, on insulin-signaling and glucose metabolism, the underlying mechanisms are not completely understood. In this study, two-dimensional-gel electrophoresis, massspectrometry and MSACOT-analyses were used to identify and characterize novel proteins modulated by hemin in spontaneoushypertensive rat (SHR), a model of e Read More

Diabetes is a complex endocrine/metabolic disease with many related complications including micro-vascular and macrovascular problems such as cardiomyopathy, nephropathy, neuropathy and retinopathy. Generally, type-1 diabetes is caused by autoimmune- mediated destruction of pancreatic beta cells leading to insulin deficiency. This is usually accompanied by dyslipidemia, enhanced hyperglycemia-mediated oxida Read More

The histamine H4 receptor (H4R), recently cloned and identified, is a G-protein coupled histamine receptor family expressed in immune cells which plays an important role in inflammation. Recent data evidentiated that H4R antagonists can decrease airway inflammation and hyperreactivity in animal models of asthma. In the present study we evaluated the effect of the selective H4R antagonist JNJ7777120 (JNJ) in carrageenan- Read More

Cardiac ischemia, followed by reperfusion, often results in the development of cardiac contractile dysfunction that limits the recovery prognosis of patients. The current goal of pharmacological therapy in the course of ischemic heart disease is to improve the oxygen supply/demand ratio for the heart. Cardiac contractile proteins such as myosin light chain 1 and 2 (MLC1 and MLC2) and troponin I, play a significant role in the regul Read More

The pathophysiology of endotoxic shock is complex. This review emphasizes the role of reactive oxygen species (ROS) in the pathophysiology of endotoxic shock and the effectiveness of flaxseed in amelioration of the deleterious effects of endotoxic shock on the cardiovascular function and health of the tissue. Endotoxic shock is associated with reduction in the cardiac function measured by cardiac index and left ventricular Read More

Hypertension is a complex interplay of interrelated etiologies, and the leading risk factor for many cardiovascular morbidity and mortality worldwide. Cardinal pathophysiological features of hypertension include enhanced vascular inflammation, vascular remodeling, vascular contractility and increased oxidative stress. In response to oxidative, inflammatory or other noxious stimuli, many physiological pathway Read More

The increased prevalence of diabetes and associated complications presents a major health risk worldwide, and requires an efficient management protocol. Type-1 and type-2 diabetes have several common pathophysiological denominators including hyperglycemia, elevated oxidative stress, increased inflammation and apoptosis. These pathological factors are implicated in the progression and worsening of the disease, and t Read More

In order to maintain an ideal body weight, an organism must balance energy intake with energy expenditure. It is well known that metabolic signals derived in the periphery act in well-defined hypothalamic and brainstem neuronal circuits to control energy homeostasis. As such, peripheral signals that convey information regarding nutritional and metabolic status of the individual must be able to access and control these neu Read More

The Acute Respiratory Distress Syndrome (ARDS) is a highly fatal pro-inflammatory oxidative respiratory disease. Relatively recently, the modulating effects of chronic inflammatory processes on ARDS susceptibility have been recognized in a number of clinical studies. Herein, we briefly review some of the chronic conditions that have been reported to increase (cigarette smoking and alcohol abuse) or decrease (di Read More

The growing incidence of obesity and related complications such as cardiomyopathy and nephropathy remains a global health challenge. Many pathophysiological factors including inflammation, oxidative stress and endothelial dysfunction are implicated in obesity- induced abnormalities in the heart and kidney. Moreover, obesity and nutrient-overload are associated with the activation of different inflammatory/oxidative sign Read More