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Article

An Untargeted Lipidomic Analysis Reveals Depletion of Several Phospholipid Classes in Patients with Familial Hypercholesterolemia on Treatment with Evolocumab

1
Fondazione Edmund Mach Research and Innovation Centre, Food Quality and Nutrition Department, Via E. Mach, 1, 38010 S. Michele all’Adige, Italy
2
Dipartimento di Farmacia, Università degli Studi di Napoli “Federico II”, 80131 Napoli, Italy
3
CEINGE-Biotecnologie Avanzate, Università degli Studi di Napoli, 80131 Napoli, Italy
4
Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli “Federico II”, 80131 Napoli, Italy
5
Centro Cardiologico Monzino, IRCCS, 38010 Milano, Italy
6
Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli “Federico II”, 80131 Napoli, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Willibald Wonisch
Biomedicines 2021, 9(12), 1941; https://doi.org/10.3390/biomedicines9121941
Received: 15 November 2021 / Revised: 13 December 2021 / Accepted: 14 December 2021 / Published: 17 December 2021
(This article belongs to the Section Molecular and Translational Medicine)
Rationale: Familial hypercholesterolemia (FH) is caused by mutations in genes involved in low-density lipoprotein cholesterol (LDL-C) metabolism, including those for pro-protein convertase subtilisin/kexin type 9 (PCSK-9). The effect of PCSK-9 inhibition on the plasma lipidome has been poorly explored. Objective: Using an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, the plasma lipidome of FH subjects before and at different time intervals during treatment with the PCSK-9 inhibitor Evolocumab was explored. Methods and Results: In 25 FH subjects, heterozygotes or compound heterozygotes for different LDL receptor mutations, untargeted lipidomic revealed significant reductions in 26 lipid classes belonging to phosphatidylcholine (PC), sphingomyelin (SM), ceramide (CER), cholesteryl ester (CE), triacylglycerol (TG) and phosphatidylinositol (PI). Lipid changes were graded between baseline and 4- and 12-week treatment. At 12-week treatment, five polyunsaturated diacyl PC, accounting for 38.6 to 49.2% of total PC at baseline; two ether/vinyl ether forms; seven SM; five CER and glucosyl/galactosyl-ceramide (HEX-CER) were reduced, as was the unsaturation index of HEX-CER and lactosyl—CER (LAC-CER). Although non quantitative modifications were observed in phosphatidylethanolamine (PE) during treatment with Evolocumab, shorter and more saturated fatty acyl chains were documented. Conclusions: Depletion of several phospholipid classes occurs in plasma of FH patients during treatment with the PCSK-9 inhibitor Evolocumab. The mechanism underlying these changes likely involves the de novo synthesis of SM and CER through the activation of the key enzyme sphingomyelin synthase by oxidized LDL and argues for a multifaceted system leading to vascular improvement in users of PCSK-9 inhibitors. View Full-Text
Keywords: PCSK-9; untargeted lipidomics; familial hypercholesterolemia PCSK-9; untargeted lipidomics; familial hypercholesterolemia
MDPI and ACS Style

Anesi, A.; Di Minno, A.; Calcaterra, I.; Cavalca, V.; Tripaldella, M.; Porro, B.; Di Minno, M.N.D. An Untargeted Lipidomic Analysis Reveals Depletion of Several Phospholipid Classes in Patients with Familial Hypercholesterolemia on Treatment with Evolocumab. Biomedicines 2021, 9, 1941. https://doi.org/10.3390/biomedicines9121941

AMA Style

Anesi A, Di Minno A, Calcaterra I, Cavalca V, Tripaldella M, Porro B, Di Minno MND. An Untargeted Lipidomic Analysis Reveals Depletion of Several Phospholipid Classes in Patients with Familial Hypercholesterolemia on Treatment with Evolocumab. Biomedicines. 2021; 9(12):1941. https://doi.org/10.3390/biomedicines9121941

Chicago/Turabian Style

Anesi, Andrea, Alessandro Di Minno, Ilenia Calcaterra, Viviana Cavalca, Maria Tripaldella, Benedetta Porro, and Matteo Nicola Dario Di Minno. 2021. "An Untargeted Lipidomic Analysis Reveals Depletion of Several Phospholipid Classes in Patients with Familial Hypercholesterolemia on Treatment with Evolocumab" Biomedicines 9, no. 12: 1941. https://doi.org/10.3390/biomedicines9121941

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