Mechanisms of spinal cord injury-induced increasd cardiovascular risk

Abstract

Several data have shown that subjects with spinal cord injury (SCI) exhibit increased atheroscleroic burden and worse left ventricular diastolic function in comparison with able-bodied subjects. These findings were independent of traditional risk factors, such as age, systemic hypertension, body mass index, metabolic alterations, smoking and serum levels of inflammatory markers. Conversely, subclinical atherosclerosis in normotensive subjects with SCI present significant correlation with diastolic blood pressure measured by Ambulatory Blood Pressure Monitoring (ABPM), suggesting that vascular/inflammatory cells of these individuals might be more sensitive to hemodynamic/mechanical stimuli. In addition, several lines of evidence have suggested that SCI-induced cardiovascular alterations may be related to extreme physical inactivity. These data point toward chronic SCI as a unique model in human beings in order to study the physiopathology of atherosclerosis and left ventricular diastolic dysfunction. The aim of this study is to investigate the potential mechanisms involved in SCI-induced atherogenesis and diastolic dysfunction. In this regard, we will evaluate the plasmatic expression/activity of metalloproteinases and the plasmatic concentration of oxidated-LDL renin, angiotensin II and cathecolamines and will assess their correlations with carotid intima-media thickness (IMT) and echocardiographic parameters in able-bodied subjects, sedentary SCI subjects and SCI athletes. In addition, we will evaluate the effects of mechanical stretch on the activation of monocytes harvested from peripheral blood and will correlate the magnitude of this activation with the carotid IMT of able-bodied and SCI subjects.