Characterizing the role of pulmonary veins in pulmonary hypertension

Pulmonary veins (PVs) transport oxygenated blood from lungs back to the heart. Small PVs can play a crucial role in the pathogenesis of pulmonary hypertension. Studies have also shown PV remodeling in pulmonary hypertension and heart failure. However, unlike pulmonary arteries (PAs), which have been a major focus of pulmonary vascular studies, the signaling mechanisms in PVs have not been investigated under normal conditions and in pulmonary hypertension. We hypothesized that the vascular wall composition and cellular signaling mechanisms in PVs are distinct from PAs. We imaged 4th order PVs (~ 50 mm) from C57BL6 mice using spinning disk confocal imaging along the z-axis. In direct contrast to PAs, where a single endothelial cell (EC) layer is surrounded by alpha actin-positive smooth muscle cells (SMCs), PV walls did not show SMCs. Cardiac troponin C staining of PVs identified cardiac myocyte-like (CML) cells with striations surrounding the EC layer. The CML layer was not observed in small PAs, vena cava, and mesenteric veins. Confocal calcium imaging showed spontaneous calcium signals in CML cells from PVs that were inhibited by ryanodine (1 mM), a ryanodine receptor inhibitor. Cannulated PVs in pressure myography experiments showed spontaneous pulsatile constrictions, which were also inhibited by ryanodine. Collectively, our results suggest that ryanodine receptor calcium signals in CML cells underlie spontaneous contractions in small PVs. Our findings also indicate that signaling mechanisms in CML cells could be potential targets for therapy in pulmonary hypertension. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.