Altered thrombopoiesis in spontaneously hypertensive rats

Platelet hyperreactivity is a risk factor for cardiovascular disease development and mortality in hypertensive patients. Although several studies have linked platelet hyperreactivity with increased bone marrow thrombopoiesis, extramedullary thrombopoiesis remains highly unexplored in hypertension and other cardiovascular diseases. Here, we investigated thrombopoiesis-related parameters in the bone marrow, spleen, and lungs of 5-week-old spontaneously hypertensive rats (SHR) and their normotensive counterparts, Wistar Kyoto rats by quantitative histological imaging, flow cytometry, and enzyme-linked immunoassays. Flow cytometry assays and quantitative histological imaging strongly suggest that thrombocytosis in SHR is caused solely by bone marrow thrombopoiesis. Moreover, analysis of the lungs showed a significant decrease in the density of megakaryocyte and CKIT^pos/CD41^pos cells, suggesting potential implications for lung megakaryopoiesis of SHR rats. Finally, while IL6 levels increased by twofold in the bone marrow, TPO levels decreased in both the bone marrow and serum of SHR rats. Overall, our results raise the question of whether pulmonary and bone marrow thrombopoiesis may regulate each other through TPO-based feedback, posing key questions about platelet biology under steady state and pathological conditions.