Context: Short small-for-gestational-age (SGA) children have an increased systolic blood pressure (BP) that decreases during long-term GH treatment. The underlying mechanism is still unknown. Matrix metalloproteinases (MMPs) are zinc-dependent endoproteinases that are involved in the remodelling of the extracellular matrix (ECM) and are thought to play a role in atherosclerosis. High MMP-9 levels are found in hypertensive patients and predict cardiovascular mortality. Objectives: To investigate whether GH treatment affects plasma MMP-9 levels in short SGA children and whether these are related to BP. Design: Case-control study. Intervention: GH treatment vs. no treatment during 36 months. Patients: Thirty-eight short SGA children receiving GH treatment vs. 17 sex- and age-matched untreated short SGA controls. Outcome measure: Plasma MMP-9 levels and BP were measured at baseline, and after 6, 12 and 36 months of study. Results: MMP-9 decreased significantly during 3 years of GH treatment but remained similar in untreated SGA controls. After 3 years of GH treatment, MMP-9 levels were significantly lower in the GH group than in the untreated SGA controls. Systolic BP SDS significantly decreased in the GH group but remained unaltered in the untreated SGA controls. MMP-9 levels did not correlate with systolic or diastolic BP. Conclusions: Plasma MMP-9 levels and systolic BP SDS decreased to almost 50% of baseline values in the GH group but remained unchanged in untreated SGA controls. Our data indicate that GH has a positive effect on both MMP-9 levels and systolic BP SDS.,
Clinical Endocrinology
Erasmus MC: University Medical Center Rotterdam

Willemsen, R.H, van Dijk, M, de Kort, S.W.K, van Toorenenbergen, A.W, & Hokken-Koelega, A.C.S. (2008). Plasma matrix metalloproteinase-9 levels and blood pressure in short children born small for gestational age and effects of growth hormone treatment. Clinical Endocrinology, 69(2), 264–268. doi:10.1111/j.1365-2265.2008.03224.x