ABSTRACT
AIM: Peripheral artery disease results in impaired blood flow to the extremities, most often as a consequence of atherosclerotic disease. The hallmark of atherosclerosis is chronic inflammation in the vessel wall. The renin-angiotensin and endothelin systems are considered important pathophysiological effectors. Midkine, a multifunctional cytokine, fulfils different roles in inflammation and promotion of neoangiogenesis. The aim of this study was to assess whether circulating midkine serum levels in patients with peripheral artery disease correlate with established atherosclerosis risk factors, as well as titers of functional autoantibodies directed against receptors of the renin-angiotensin and endothelin system. METHODS: Clinical data, laboratory values and serum samples from 118 patients operated on for severe peripheral artery disease, and from 100 healthy blood donors were collected. Serum samples were analysed for midkine concentrations as well as autoantibody titers against angiotensin II type 1 and endothelin-1 type A receptors. RESULTS: Midkine values were significantly higher in the study population than in healthy controls (P<0.001). Circulating midkine levels did not correlate with neither of the traditional risk factors age, sex, obesity, smoking, hypertension, high cholesterol levels, or diabetes mellitus. An unexpected inverse correlation was found with the autoantibodies against angiotensin II type 1 receptor (P<0.05) and endothelin-1 type A receptor (P<0.01). CONCLUSION: The high levels of midkine in severe peripheral artery disease patients introduce this cytokine as a possible novel effector in the advanced atherosclerotic process. These results also suggest a functional link between vascular receptor autoantibody formation and down-regulated midkine serum levels, that may be relevant in the pathogenesis of clinically relevant peripheral artery occlusive disease.
