Endothelial function and arterial stiffness in sickle-thalassemia patients.

BACKGROUND: Homozygous sickle-cell anemia and beta-thalassemia are characterized by impaired endothelial function, while data on arterial stiffness have hitherto been conflicting. We sought to investigate aortic elastic properties and endothelial function in sickle-thalassemia, which combines molecular and clinical features of the above conditions. METHODS AND RESULTS: Forty-seven sickle-thalassemia patients, younger than 45 years, with preserved left ventricular (LV) function and no history of smoking, systemic or pulmonary hypertension, diabetes mellitus, dyslipidemia or thyroid disease, along with 40 healthy controls were studied. Aortic strain, distensibility and stiffness index were calculated by echocardiographically-obtained aortic root diameters. Brachial artery endothelial function was assessed by ultrasonographic evaluation of flow-mediated dilatation (FMD) and nitrate-mediated dilatation (NMD). Left ventricle was assessed by echocardiography. Patients had an impaired FMD (4.2+/-2.9% versus 9.2+/-3.8% in controls, p<0.001) with a preserved NMD (16.9+/-5.6% versus 15.2+/-4.8% in controls, p>0.05). Aortic strain and distensibility were lower and aortic stiffness index was higher in patients compared to controls (8.1+/-4.6 versus 5.8+/-2.9, p<0.01). Indexed LV diameters and mass were higher in patients. Systolic LV function was preserved, while 14.9% of patients had an impaired relaxation transmitral inflow pattern. Patients' LV mass index and diastolic mitral E wave deceleration time were positively correlated with aortic stiffness index (p<0.001). CONCLUSION: Sickle-thalassemia is characterized by a complex vasculopathy, consisting of endothelial dysfunction and increased arterial stiffness, with a global effect on cardiovascular function.

Evidence for the involvement of cannabinoid receptors' polymorphisms in the pathophysiology of human diseases.

INTRODUCTION: Considerable progress has been made, over the last years, in understanding the role of the endocannabinoid system (ES) in regard to its role in a variety of physiological processes including nociception (pain-sensation), appetite, lipid metabolism, gastrointestinal motility, cardiovascular modulation, motor activity, and memory. Furthermore, ES is strongly associated with human behavior and the skeletal ES is of major importance. ES is comprised of cannabinoid receptors (CB1 and CB2), their endogenous ligands (endocannabinoids) and proteins responsible for their metabolism. AREAS COVERED: To summarize and present all the existing literature that associate CB receptors' polymorphisms with behavior and disease in different populations, as well as its possible therapeutic perspectives. A literature review presenting the most recent data in terms of ES and the latest knowledge regarding the involvement of genetic polymorphisms of cannabinoid receptors in a variety of human diseases and psychiatric and neurological disorders. EXPERT OPINION: The ES is an emerging target for drug discovery, because it is involved in the regulation of many cellular and physiological functions. The modulation of the ES by selective agonists or antagonists may hold tremendous therapeutic potential in various conditions mentioned in this review. However, further information is still required before the ES is completely comprehended.