PB0855 - Platelet dysfunction in HFpEF patients: plasma and whole blood measurements

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Giorgia D'Italia

PhD student
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
maastricht, Limburg, Netherlands

Co-Author(s)

Daniëlle M. Coenen, MSc, PhD

Postdoctoral Research Fellow
Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA
Lexington, Kentucky, United States
TL

Titus Lemmens

PhD candidate
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University
Maastricht, Limburg, Netherlands
SW

Simone Wielders

Education-/Research Officer
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
AA

Ahmad Al-Abadi

Student
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
ST

Samah Toutouh

Student
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
JF

Joël Franssen

Student
Department of Cardiology, Maastricht University Medical Centre (MUMC+), Maastricht, Netherlands
Maastricht, Limburg, Netherlands
SM

Sanne Mourmans

PhD student
Department of Cardiology, Maastricht University Medical Centre (MUMC+), Maastricht, Netherlands
Maastricht, Limburg, Netherlands
BT

Bibian Tullemans

PhD
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
JW

Jerremy Weerts

MD, PhD student
Department of Cardiology, Maastricht University Medical Centre (MUMC+), Maastricht, Netherlands
Maastricht, Limburg, Netherlands
AB

Arantxa Barandiaran Aizpurua

MD
Department of Cardiology, Maastricht University Medical Centre (MUMC+), Maastricht, Netherlands
Maastricht, Limburg, Netherlands
Vv

Vanessa van Empel

Associate Professor
Department of Cardiology, Maastricht University Medical Centre (MUMC+), Maastricht, Netherlands
Maastricht, Limburg, Netherlands
BS

Blanche Schroen

Dr., Full professor
Department of Cardiology, Maastricht University Medical Centre (MUMC+), Maastricht, Netherlands
Maastricht, Limburg, Netherlands
JC

Judith Cosemans, PhD

Professor
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University
Maastricht, Limburg, Netherlands

Background: Heart failure with preserved ejection fraction (HFpEF) results from a complex interplay of systemic syndromes, that include diabetes and hypertension and are characterized by chronic low-grade inflammation and microvascular dysfunction (MVD). In recent years, the importance of platelets in vascular inflammation and endothelial dysfunction emerged, suggesting an unexplored role for platelets in MVD. However, the role of platelets in HFpEF is still poorly examined.

Aims: To investigate whether HFpEF patients present alterations in platelet functions.

Methods: Endothelial and platelet activation markers were measured in plasma from HFpEF patients with and without type 2 diabetes mellitus (T2DM) and age- and sex-matched hypertensive controls. Moreover, platelet integrin αIIbβ3 activation and platelet α-granule secretion were measured by flow cytometry using freshly isolated platelets from HFpEF patients (N=80) and hypertensive controls (N=25, recruitment in progress), stimulated with different agonists. Microfluidics assays with whole blood from HFpEF patients and controls were performed to measure adhesion, platelet activation markers (CD62P, fibrin(ogen), annexin A5) and thrombus growth under arterial flow conditions.

Results: Markers for endothelial cell activation, ICAM-1, VCAM-1, are increased in HFpEF patients compared to hypertensive controls, reflecting the inflammatory state in HFpEF. On the other hand, platelet activation markers, β-TG, PF4, TSP-1, are decreased, especially in HFpEF patients with type 2 diabetes mellitus. Moreover, platelets from HFpEF patients show decreased integrin αIIbβ3 activation and α-granule secretion upon stimulation with collagen-related peptide and TRAP-6, and a tendency for an overall reduction in platelet surface coverage, activation of platelets and thrombus formation under flow.

Conclusion(s): In sum, our preliminary results show endothelial cell activation and platelet dysfunction in HFpEF patients compared to hypertensive controls, suggesting a possible unrecognized role of platelets in HFpEF.