Angiostatin Levels in Systolic Heart Failure Patients with Chronic Kidney Disease

Abstract

Angiostatin levels in systolic heart failure patients with chronic kidney disease C KD is characterized by alterations in kidney function, which manifest in various ways, depending upon the underlying causes and the severity of the disease [1-3]. Heart failure (HF) with reduced ejection (HFrEF) occurs when the ejection fraction (EF) is less than 40%. When the EF is in the range of 40% to 50%, it is classified as HF with mid-range EF (HFmrEF). These conditions are considered systolic HF [4, 5]. Angiostatin is a naturally occurring protein, formed through the process of the fragmentation of plasminogen. It is a potent endogenous inhibitor of mesenchymal stem cells, endothelial cells, and angiogenesis [6]. Many studies have focused on the effect of angiostatin on endothelial cell apoptosis, though the mechanisms of action are still not yet completely understood [7, 8]. The binding of angiostatin to plasma membrane-localized adenosine triphosphate (ATP) synthase suppresses ATP metabolism in the endothelial cells, and thus downregulates en-dothelial cell proliferation [9]. Objectives: Heart failure (HF) with reduced ejection fraction (HFrEF) is defined as an ejection fraction (EF) of less than 40%. An EF of 40% to 50% is known as HF with mid-range EF, which is considered a subgroup of HF with preserved ejection fraction, rather than HFrEF. Angiostatin inhibits angiogenesis and the proliferation of mesenchymal stem cells. Though many studies in the literature have focused on the effect of angiostatin on endothelial cell apoptosis, studies about angiostatin levels in HF patients are limited. The aim of this study was to evaluate the angiostatin level in systolic HF patients with chronic kidney disease (CKD). Methods: A group of 69 individuals, consisting of patients with a diagnosis of systolic HF with CKD (n=29) and healthy (n=40) subjects, was included in the current study. Serum angiostatin, plasma N-terminal pro-brain type natriuretic peptide, and creatinine levels were assessed, and transthoracic echocardiography was performed. Results: The angiostatin level of the patient group was significantly higher than that of the control group (median: 163 ng/mL [25 th-75 th interquartile range: 48-336 ng/mL] and median: 58.14 ng/mL [25 th-75 th interquartile range: 18.1-167 ng/mL], respectively; p=0.02). The angiostatin level of HF patients receiving beta blocker therapy was significantly higher than that of the HF patients who were not taking a beta blocker (105.3 ng/mL [50.7-220.7 ng/mL] and 70.4 ng/ mL [35-224 ng/mL], respectively; p=0.02). Conclusion: To the best of our knowledge, this study is the first to examine this subject. Angiostatin may be an important marker in systolic HF patients with CKD. The use of a beta blocker may inhibit angiogenesis and induce apoptosis in HF patients with CKD. Further studies are required.