OC 10.4 - Proprotein convertase subtilisin kexin type 9 inhibitors reduce platelet nets release driver thrombosis in familial hypercholesterolemia

Saturday, June 24, 2023

13:45 – 14:00 ET

Room: 515

Session Available As: On-Demand

Presenting Author(s)

Vittoria Cammisotto, PhD

Researcher
Sapienza University of Rome,Department of Clinical Internal, Anaesthesiological and Cardiovascular Sciences
Rome, Lazio, Italy

Co-Author(s)

FB

Francesco Baratta

Medical director
Sapienza University of Rome,Department of Clinical Internal, Anaesthesiological and Cardiovascular Sciences
Rome, Lazio, Italy
Cristina Nocella, PhD

Assistant Professor
Sapienza University of Rome, Department of Clinical Internal, Anesthesiology and Cardiovascular Sciences
Rome, Lazio, Italy
SB

Simona Bartimoccia

Research Fellow
Sapienza University of Rome,Department of Clinical Internal, Anaesthesiological and Cardiovascular Sciences
Rome, Lazio, Italy
VC

Valentina Castellani

PhD student
Sapienza University of Rome, Department of General Surgery and Surgical Speciality Paride Stefanini
Rome, Lazio, Italy
LD

Laura D’Erasmo

MD
4Department of Translationaland Precision Medicine, Sapienza Universityof Rome, Rome, Italy
Rome, Lazio, Italy
CB

Cristina Barale

PhD
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
Tutin, Piemonte, Italy
RS

Roberto Scicali

MD
Department of Clinicaland ExperimentalMedicine, InternalMedicine, Universityof Catania, Catania, Italy
Catania, Sicilia, Italy
IR

Isabella Russo

PhD
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
Turin, Piemonte, Italy
FP

Francesco Purrello

MD
Department of Clinical and Experimental Medicine, Internal Medicine, University of Catania, Catania,
Catania, Sicilia, Italy
MA

Marcello Arca

MD
Department of Translationaland Precision Medicine, Sapienza Universityof Rome, Rome, Italy
Rome, Lazio, Italy
DP

Daniele Pastori

MD
Department of Clinical, InternalMedicine, Anesthesiologicaland CardiovascularSciences, Sapienza Universityof Rome, Rome, Italy
Rome, Lazio, Italy
RC

Roberto Carnevale

Associate Professor
Sapienza University of Rome, Department of Medical-Surgical Sciences and Biotechnologies
Rome, Lazio, Italy
Francesco Violi, Professor of internal medicine, Sapienza University, Rome

MD
Department of Clinical, InternalMedicine, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
Rome, Lazio, Italy
Pasquale Pignatelli, PhD

Professor
Dept. of Clinical, Internistic, Anesthesiologic and Cardiovascular Sciences, Sapienza University
Roma, Lazio, Italy

Background: Elevated levels of low-density lipoprotein-cholesterol (LDL-C) contribute to chronic systemic inflammation in heterozygous familial hypercholesterolemia (HeFH). Of note, the treatment of HeFH patients with PCSK9 inhibitor (PCSK9i) significantly reduce LDL-c levels. Moreover, neutrophil extracellular traps (NETs) release has been shown to induce activation of endothelial cells and platelets, resulting in a proinflammatory response. Thus, NETs may play a role in triggering atherosclerotic plaque formation and thrombosis.

Aims: The aim of this study is to describe the inflammatory profile of HeFH patients and explore the effect of PCSK9 inhibitor (PCSK9i) on NETs release, thrombus formation and finally, investigate the underlyng molecular mechanisms.

Methods: We studied 40 patients with heterozygous familial hypercholesterolemia (HeFH) on treatment with maximum tolerated statin dose ± ezetimibe before and after six months of PCSK9i therapy. We analysed NETs release and thrombus formation by measuring in plasma citrullination of histone H3 (CitH3) and thrombus-formation analysis system (T-TAS), respectively. Furthermore, we investigated by in vitro study if plasma post-PCSK9i reduced NETs release and thrombus formation.

Results: In vivo studies showed decreased circulating levels of CitH3 and under laminar flow platelet-dependent thrombus growth in HeFH patients after PCSK9i treatment compared to patients before treatment. In vitro study showed that plasma from HeFH patients after PCSK9i treatment decreased NETs release by neutrophils, and thrombus formation.

Conclusion(s): This study provides evidence that HeFH patients showed an increased NETs release and thrombus growth that were inhibited by the treatment with PCSK9i which may represent a novel approach to counteract inflammation and in these patients.

Learning Objectives:

to describe a mechanism involved in the thrombotic process PCSK9-mediated
to explore the effect of PCSK9 inhibitor (PCSK9i) on NETs release and thrombosis
to increase their knowledge about a novel therapeutic approach to counteract thrombotic risk in hypercholesterolemic patients.