Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology

• Published in: International journal of molecular sciences Vol. 25; no. 5; p. 2999
• Main Authors: Rossi, Rosanna, Jabrah, Duaa, Douglas, Andrew, Prendergast, James, Pandit, Abhay, Gilvarry, Michael, McCarthy, Ray, Redfors, Petra, Nordanstig, Annika, Tatlisumak, Turgut, Ceder, Erik, Dunker, Dennis, Carlqvist, Jeanette, Szikora, István, Tsivgoulis, Georgios, Psychogios, Klearchos, Thornton, John, Rentzos, Alexandros, Jood, Katarina, Juega, Jesus, Doyle, Karen M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2024; MDPI
• Subjects: acute ischemic stroke; Atherosclerosis; Biomarkers; Blood clot; Blood clots; Blood platelets; BNP; Brain; brain natriuretic peptide; Brain research; Cardiac patients; Cardiomyocytes; Cardiovascular disease; Causality; Causes and theories of causation; complications; Diseases; Ethylenediaminetetraacetic acid; Etiology; Heart Failure; Humans; Immunohistochemistry; Inflammation; Ischemia; Ischemic Stroke; Ischemic Stroke - complications; Lymphocytes; Natriuretic Peptide; Natriuretic Peptide, Brain; Natriuretic peptides; Neurologi; Neurology; Neutrophils; NT-proBNP; Patients; Peptide Fragments; Peptides; Plasma; Stroke; Stroke (Disease); Stroke - etiology; stroke biomarkers; Thrombosis; Thrombosis - complications; thrombus; Veins & arteries; Canada; United Kingdom; Ireland; stroke etiology; NT-proBNP; BNP; acute ischemic stroke; stroke biomarkers; brain natriuretic peptide; thrombus
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25052999

The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman's rho = 0.668 < 0.0001 *). We did not observe any statistically significant difference between LAA and CE clots in BNP expression (0.66 [0.13-3.54]% vs. 0.53 [0.14-3.07]%, = 0.923) or in NT-proBNP expression (0.29 [0.11-0.58]% vs. 0.18 [0.05-0.51]%, = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process.