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. 2020 Jun 19;9(6):1928.
doi: 10.3390/jcm9061928.

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

Gilda Varricchi  1   2   3   4 , Stefania Loffredo  1   2   3   4 , Leonardo Bencivenga  1   5 , Anne Lise Ferrara  1   2   3 , Giuseppina Gambino  1 , Nicola Ferrara  1 , Amato de Paulis  1   2   3 , Gianni Marone  1   2   3   4 , Giuseppe Rengo  1   6
Affiliations

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

Gilda Varricchi et al. J Clin Med. .

Abstract

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.

Keywords: IHF; NIHF; VEGFs; angiopoietins; heart failure; sPLA2.

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Conflict of interest statement

All authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(A) Plasma concentrations of angiopoietin-1 (ANGPT1) in heart failure (HF) patients and in healthy controls; (B) Plasma concentrations of ANGPT2 in HF patients and in healthy controls; (C) ANGPT2/ANGPT1 ratio in HF patients and in healthy controls. Data are shown as the median (horizontal block line), the 25th and 75th percentiles (boxes), and the 5th and 95th percentiles (whiskers) (statistical analysis was performed by a Student’s t-test). ** p < 0.01; *** p < 0.001; **** p < 0.0001.
Figure 2
Figure 2
(A) Plasma concentrations ofvascular endothelial growth factor-A (VEGF-A) in heart failure (HF) patients and in healthy controls; (B) plasma concentrations of VEGF-C in HF patients and in healthy controls; (C) plasma concentrations of VEGF-D in HF patients and in healthy controls. Data are shown as the median (horizontal block line), the 25th and 75th percentiles (boxes), and the 5th and 95th percentiles (whiskers) (statistical analysis was performed by a Student’s t-test). *** p < 0.001.
Figure 3
Figure 3
Plasma concentrations of sPLA2 activity in HF patients and in healthy controls. Data are shown as the median (horizontal block line), the 25th and 75th percentiles (boxes), and the 5th and 95th percentiles (whiskers) (statistical analysis was performed by a Student’s t-test). **** p < 0.0001.
Figure 4
Figure 4
(A) Plasma concentrations of angiopoietin-1 (ANGPT1) in ischemic (IHF) and non-ischemic (NIHF) patients, and in healthy controls; (B) plasma concentrations of ANGPT2 in IHF and NIHF patients, and in healthy controls; (C) ANGPT2/ANGPT1 ratio in IHF and NIHF patients, and in healthy controls. Data are shown as the median (horizontal block line), the 25th and 75th percentiles (boxes), and the 5th and 95th percentiles (whiskers) (statistical analysis was performed by one-way ANOVA and Bonferroni’s multiple comparison test). * p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 5
Figure 5
(A) Plasma concentrations of VEGF-A in IHF and NIHF patients and in healthy controls; (B) plasma concentrations of VEGF-C in IHF and NIHF patients and in healthy controls; (C) plasma concentrations of VEGF-D in IHF and NIHF patients and in healthy controls. Data are shown as the median (horizontal block line), the 25th and 75th percentiles (boxes), and the 5th and 95th percentiles (whiskers) (statistical analysis was performed by one-way ANOVA and Bonferroni’s multiple comparison test). * p < 0.05
Figure 6
Figure 6
Plasma concentrations of sPLA2 activity in IHF and NIHF patients and in healthy controls. Data are shown as the median (horizontal block line), the 25th and 75th percentiles (boxes), and the 5th and 95th percentiles (whiskers) (statistical analysis was performed by one-way ANOVA and Bonferroni’s multiple comparison test). ** p < 0.01; *** p < 0.001.
Figure 7
Figure 7
(A) Correlations between the plasma concentrations of ANGPT2 and ANGPT1 in NIHF patients; (B) correlation between circulating sPLA2 activity and the concentration of ANGPT1 in NIHF patients; (C) correlation between the plasma concentration of sPLA2 activity and ANGPT2 in NIHF patients; (D) correlation between the plasma concentration of sPLA2 activity and the ANGPT2/ANGPT1 ratio in NIHF patients. Spearman’s correlation coefficients (r) were calculated and are shown in the panels.
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