Acute effects of insulin-like growth factor-1 and recombinant growth hormone on liprotein(a) levels in baboons

Abstract

Elevated lipoprotein(a) [Lp(a)] is an established factor for coronary artery disease (CAD) that acts possibly by increasing cholesterol deposition in arterial wall and promoting thrombosis. The only known Lp(a)-lowering agents, niacin and neomycin, often produce intolerable side effects. We observed that administration of growth hormone (GH) increases but insulin-like growth factor-1 (IGF-1) decreases Lp(a) levels in patients with GH deficiency. To explore the mechanisms for the hormonal effects and to search for an effective pharmaceutical agent, we examined the suitability of the baboon as an animal model by investigating the effects of GH and IGF-1 on Lp(a). We selected 5 baboons with high (group 1) and 5 with low (group 2) Lp(a) levels. Group 1 baboons first received a bolus subcutaneous injection of IGF-1 (300 [mu ]g/kg body weight). After a period of 7 days, they were given a bolus infusion of recombinant human (rh)GH (300 [mu ]g/kg body weight). For group 2 baboons, the order of injection was reversed, and rhGH was given first and followed by IGF-1. Blood samples were collected during the day before and for 3 days following each injection. Levels of plasma Lp(a), insulin, GH, and IGF-1 were measured for each time point. While rhGH appeared not to raise Lp(a) levles among baboons with extremely low levels (6.8 [plusmn] 1.1 mg/dL at baseline v 6.6 [plusmn] 0.9 mg/dL, n = 5), IGF-1 significantly reduced Lp(a) levels among those with high levels within 2 hours of injection (57.0 [plusmn] 6.6 mg/dL v 37.4 [plusmn] 6.2 mg/dL, or a 34% reduction, n = 3, P = .013). Our study for the first time demonstrated that IGF-1 can lower plasma Lp(a) levels by more than 30% within 2 hours in baboons and the effects are sustained for at least 1 week. The effect is likely mediated through increased Lp(a) degradation, but the responsible organs remain to be identified. On the other hand, rhGH appeared to have no effect on those animals with very low Lp(a) levels.