Hepatocyte growth factor as a potential index of complication in diabetes mellitus

Objective Diabetes mellitus (DM), characterized by the premature developmen t of microvascular and macrovascular disease, shows a loss of vasodilatory properties of resistance vessels. However, the mechanisms of endothelial dy sfunction in diabetes have not yet been clarified. Hepatocyte growth factor (HGF) in vascular cells was down-regulated by high glucose levels, potenti ally accelerating the endothelial dysfunction in DM. In this study, the ser um HGF level was measured to investigate further the role of HGF in DM. Methods Tissue and circulating HGF levels were measured in the KKA(y) mouse , a rodent model of noninsulin-dependent diabetes mellitus (NIDDM), and lea n C57 BL control mice. Then, serum HGF concentrations were measured in NIDD M patients without liver, kidney or lung damage. For the study of serum HGF concentration, 30 normotensive and age-matched 58 DM patients were studied . The 58 DM patients were divided into 26 patients without hypertension and 32 patients with hypertension [22 patients without hypertensive complicati ons (WHO I) and 10 patients with hypertensive complications (WHO II + III)] . Results The serum HGF concentration in KKA(y) mice was significantly lower than that in control mice (P< 0.01), at 14 weeks of age when they exhibit f eatures of diabetes. Similarly, tissue HGF concentrations in the heart and kidney were decreased significantly in KKA(y) mice compared with control C5 7 BL mice (P< 0.05). The serum HGF concentration showed a significant negat ive correlation with hemoglobin (Hb) A,, concentration (P< 0.01, r = -0.41) . Since the serum HGF concentration is a potential index of the severity of hypertension, the serum levels of HGF in DM patients without and with hype rtension were examined. The serum HGF concentration in DM patients without hypertension was significantly lower than that in normal subjects (P < 0.05 ), whereas that in DM patients with hypertension was significantly higher t han that in normal subjects (P< 0.01). Moreover, the serum HGF concentratio n in DM patients with hypertensive complications was further higher than th at in others (P< 0.01). Conclusion The present data showed that serum, cardiac and renal HGF concen trations in KKA(y) mice were significantly decreased compared with control mice. Therefore, a decrease in local HGF may be a trigger of endothelial dy sfunction in DM. Clinical data also demonstrated a significant negative cor relation between serum HGF and HbA(lc) concentrations in diabetic patients without complications. In contrast, the serum concentration of HGF was sign ificantly elevated depending on the severity of hypertension. These results suggest that HGF may be a new index of complications such as hypertension in DM. J Hypertens 1998, 16:2019-2026 (C) 1998 Lippincott Williams & Wilkin s.