Clinical significance of Apela in acute cardio-renal insuffiency of chronic heart failure.

INTRODUCTION: Apela has a wide range of biological effects on the cardiovascular system, but the changes and significance of endogenous Apela in patients with chronic heart failure (CHF) and acute deterioration of cardiac and renal function are unclear.

METHODS: A total of 69 patients with stable CHF combined with well-preserved renal function were enrolled and followed for 12 months. The effects of Apela on human renal glomerular endothelial cells (hRGEC), human glomerular mesangial cells (hGMC) and human renal tubular epithelial cells (HK-2) were observed.

RESULTS: Serum Apela concentration was positively correlated with NYHA class (r = 0.711) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration (r = 0.303) but negatively correlated with left ventricular ejection fraction (LVEF) (r = -0.374) and 6-minute walk distance (r = -0.860) in patients with stable CHF. Twenty-one patients experiencing deterioration of renal and cardiac function were diagnosed with cardiorenal syndrome (CRS) during the follow-up period. In addition, the serum Apela, as well as the difference in Apela between stable and worsening phases (ΔApela), was correlated with the estimated glomerular filtration rate (eGFR) and ΔeGFR in patients with CRS. Apela significantly inhibited the up-regulated expression of MCP-1 and TNF-α induced by angiotensin II (AngII) in hRGEC, hGMC and HK-2 cells. Apela inhibited the adhesion of THP-1 cells to hRGEC and promoted the tubular formation of hRGEC. Moreover, Apela enhanced the expression of MMP-9 in hGMC but inhibited the up-regulated expression of α-SMA and vimentin in HK-2 cells by AngII.

CONCLUSION: This study suggests that the level of Apela can be used to diagnose heart failure and assess the severity of cardiac dysfunction in patients with stable CHF, and its dynamic changes can be used to evaluate the damage to renal function in patients with CRS. Apela plays multiple protective effects on renal cells, highlighting its clinical application prospect in the prevention and treatment of CRS.