Experimental study on arterial compliance and urinary excretionof TGF-BETA in a group of small-for-gestational-age children-adolescents

Background: Intrauterine Growth Restriction play a powerful role in influencing later susceptibility to certain chronic diseases. Endothelium plays a key role in the development of atherosclerosis. Endothelial dysfunction and arterial stiffness are early events in the development of cardiovascular diseases. TGF-a triggers a profibrotic response inducing the synthesis of extracellular matrix, retards its degradation, and stimulates the synthesis of integrin. To study vascular tree in small for gestational age adolescents (SGA) versus appropriate for gestational age (AGA) subjects, we monitored basal and postischemic vascular compliance in 67 adolescents; in 30 children-adolescents we studied the urinary excretion of TGF-a before and after ischemic stimulus. Methods and Results: Arterial elasticity, by pulse wave analysis was assessed in 52 SGA and in 15 AGA, at radial level, before and after an ischemic stimulus. TGF-a excretion was detected in 14 SGA and in 16 AGA (ELISA-Quantikine R&D Systems). In SGA we observed significant increase of Systolic (+7.6 mm Hg), Pulse (+2.29 mm Hg), Diastolic Blood Pressure (+4,23) and of Vascular Resistances (+151); the elasticity of large (-2.16) and small (-1.53) vessels was worse in SGA group. After ischemia we noticed a greater vasodilation: higher decrease in Systolic (-4.1 in SGA versus -2.1 in AGA), diastolic pressure (-1.57 and -1.3 in SGA and AGA) and vascular resistances (-117 in SGA and -116 in AGA); we observed a greater increase in macrovascular (+1.73 in SGA +0.4 in AGA) and microvascular elasticity (+0.82 in SGA, +0.35 in AGA). The basal urinary excretion of TGF-a increased in SGA group and doubled after ischemic stimulus versus AGA adolescents; these post-ischemic response were significant (p = 0.01). Conclusions: Our results shows that in SGA group there are some evidences of a very precocious markers of endothelial dysfunction that is associated with a raised synthesis and release of a profibrotic agent as TGF-a, that could play a pathogenetic role in the development of arterial stiffness.