Homoarginine reduces neointimal hyperplasia in balloon-injured rat carotid arteries

BACKGROUND: Homoarginine, an L-arginine homologue, is a cationic amino acid derived from lysine. Its physiological role is unknown, but the structural similarity to L-arginine suggests that it may be an alternative substrate for nitric oxide synthase. Data from the Ludwigshafen Risk and Cardiovascular Health Study have shown that low circulating homoarginine is an independent risk factor for all-cause and cardiovascular mortality. Recently, genome-wide association studies identified three genomic loci significantly related to serum levels of homoarginine. The strongest association was observed on chromosome 15 at the L-arginine:glycine amidinotransferase locus, the enzyme responsible for the synthesis of homoarginine. AIM: The purpose of this study was to evaluate the effect of homoarginine on neointimal formation in a rat model of balloon injury. METHODS: Thirty-six male Sprague-Dawley rats underwent endothelial injury at the level of the left carotid followed by the insertion of a cannula into the right jugular vein. The cannula was connected to an Alzet® pump containing saline, L-arginine (30 mg/kg per day, used as a positive control) or homoarginine (30 mg/kg per day). Fourteen days after balloon injury, blood was collected and left carotids were harvested for histological analyses. Systolic blood pressure was measured before and at the end of drug treatments. RESULTS: As expected, L-arginine administration significantly reduced the carotid intimal/medial area ratio compared to that of controls (0.69±0.40 vs 1.33±0.67, p<0.05). Homoarginine-treated rats also showed a significant reduction of the vessel intimal/medial area ratio versus controls (0.71±0.43 vs 1.33±0.67, p<0.05). No changes in systolic blood pressure were detected by treatment in all groups. Plasma L-arginine concentration was significantly increased in both L-arginine- and homoarginine-treated rats compared to controls (p<0.05). CONCLUSIONS: Our study shows that homoarginine is able to inhibit neointima formation in balloon-injured rat carotid arteries. Moreover, our data indicate that this effect could be due, at least in part, to an increased availability of L-arginine.