Angiopoietins, Vascular Endothelial Growth Factors and Secretory Phospholipase A₂ in Ischemic and Non-Ischemic Heart Failure

• Main Authors: Gilda Varricchi, Stefania Loffredo, Leonardo Bencivenga, Anne Lise Ferrara, Giuseppina Gambino, Nicola Ferrara, Amato de Paulis, Gianni Marone, Giuseppe Rengo
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: Journal of Clinical Medicine
• Subjects: angiopoietins; heart failure; VEGFs; sPLA₂; IHF; NIHF
• Online Access: https://www.mdpi.com/2077-0383/9/6/1928

Heart failure (HF) is a growing public health burden, with high prevalence and mortality rates. In contrast to ischemic heart failure (IHF), the diagnosis of non-ischemic heart failure (NIHF) is established in the absence of coronary artery disease. Angiopoietins (ANGPTs), vascular endothelial growth factors (VEGFs) and secretory phospholipases A₂ (sPLA₂s) are proinflammatory mediators and key regulators of endothelial cells. In the present manuscript, we analyze the plasma concentrations of angiogenic (ANGPT1, ANGPT2, VEGF-A) and lymphangiogenic (VEGF-C, VEGF-D) factors and the plasma activity of sPLA₂ in patients with IHF and NIHF compared to healthy controls. The concentrations of ANGPT1, ANGPT2 and their ratio significantly differed between HF patients and healthy controls. Similarly, plasma levels of VEGF-D and sPLA₂ activity were higher in HF as compared to controls. Concentrations of ANGPT2 and the ANGPT2/ANGPT1 ratio (an index of vascular permeability) were increased in NIHF patients. VEGF-A and VEGF-C concentrations did not differ among the three examined groups. Interestingly, VEGF-D was selectively increased in IFH patients compared to controls. Plasma activity of sPLA₂ was increased in IHF and NIHF patients compared to controls. Our results indicate that several regulators of vascular permeability and smoldering inflammation are specifically altered in IHF and NIHF patients. Studies involving larger cohorts of these patients will be necessary to demonstrate the clinical implications of our findings.