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Volume 14
Issue 6
10.3390/biomedicines14061203
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Review

The Role of Platelets in Pulmonary Hypertension: From Activation to Pulmonary Vascular Remodeling—A Review Article

by
Patrycja Wszelaki
1,
Aleksandra Karczmarska
1,
Szymon Szymoniuk
1,
Grzegorz Grześk
2,
Zbigniew Włodarczyk
3 and
Joanna Sikora
1,*
1
Research and Education Unit for Experimental Biotechnology, Department of Transplantology and General Surgery, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland
2
Department of Cardiology and Clinical Pharmacology, Collegium Medicum, Nicolaus Copernicus University, 85-168 Bydgoszcz, Poland
3
Department of Transplantology and General Surgery, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland
*
Author to whom correspondence should be addressed.
Biomedicines 2026, 14(6), 1203; https://doi.org/10.3390/biomedicines14061203
Submission received: 24 March 2026 / Revised: 11 May 2026 / Accepted: 18 May 2026 / Published: 27 May 2026
(This article belongs to the Special Issue Platelets in Human Health and Diseases)
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Abstract

The article presents the results of a structured literature review of the past decade and focuses on the crucial role of platelets in the pathogenesis of pulmonary arterial hypertension (PAH). It explores how endothelial dysfunction initiates early prothrombotic signals that activate platelets, which, in response, adopt a pro-inflammatory phenotype, release cytokines and chemokines, and form aggregates with leukocytes, thereby modulating their migration and activity. A key feature of PAH is the “platelet paradox,” in which chronic in vivo activation coexists with reduced ex vivo reactivity due to functional exhaustion. Prolonged stimulation and disease progression lead to complex hemostatic dysregulation, characterized by heterogeneity in platelet phenotypes. At the same time, platelets undergo immunometabolic reprogramming, with a predominance of glycolysis, over oxidative phosphorylation, mitochondrial dysfunction, altered fatty acid oxidation (FAO), increased lactate production, and enhanced vesicle release. These phenomena sustain inflammation and promote pulmonary vascular remodeling. This study aims to review the current mechanisms of immunometabolic platelet activation in pulmonary arterial hypertension. It primarily focuses on platelet aspects as key elements in disease progression and as potential sources of new biomarkers and therapeutic targets.
Keywords: pulmonary arterial hypertension; platelets; vascular inflammation; metabolic reprogramming; platelet–leukocyte aggregates; platelet paradox pulmonary arterial hypertension; platelets; vascular inflammation; metabolic reprogramming; platelet–leukocyte aggregates; platelet paradox

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MDPI and ACS Style

Wszelaki, P.; Karczmarska, A.; Szymoniuk, S.; Grześk, G.; Włodarczyk, Z.; Sikora, J. The Role of Platelets in Pulmonary Hypertension: From Activation to Pulmonary Vascular Remodeling—A Review Article. Biomedicines 2026, 14, 1203. https://doi.org/10.3390/biomedicines14061203

AMA Style

Wszelaki P, Karczmarska A, Szymoniuk S, Grześk G, Włodarczyk Z, Sikora J. The Role of Platelets in Pulmonary Hypertension: From Activation to Pulmonary Vascular Remodeling—A Review Article. Biomedicines. 2026; 14(6):1203. https://doi.org/10.3390/biomedicines14061203

Chicago/Turabian Style

Wszelaki, Patrycja, Aleksandra Karczmarska, Szymon Szymoniuk, Grzegorz Grześk, Zbigniew Włodarczyk, and Joanna Sikora. 2026. "The Role of Platelets in Pulmonary Hypertension: From Activation to Pulmonary Vascular Remodeling—A Review Article" Biomedicines 14, no. 6: 1203. https://doi.org/10.3390/biomedicines14061203

APA Style

Wszelaki, P., Karczmarska, A., Szymoniuk, S., Grześk, G., Włodarczyk, Z., & Sikora, J. (2026). The Role of Platelets in Pulmonary Hypertension: From Activation to Pulmonary Vascular Remodeling—A Review Article. Biomedicines, 14(6), 1203. https://doi.org/10.3390/biomedicines14061203

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