Pulmonary Artery Smooth Muscle
As with ASM, intracellular Ca2+ plays a major role in pulmonary artery smooth muscle (PASM) contraction. Devastating diseases such as pulmonary hypertension involve, at least in part, altered Ca2+ regulation and changes in cell proliferation in the lung vasculature. Again, drugs used in anesthesia and critical care affect PASM tone. The laboratory is currently focused on two aspects of Ca2+ regulation (and dysregulation) in PASM.
- Neurotrophins. Recent evidence suggests that neurotrophins and their receptors are expressed in pulmonary artery smooth muscle. Furthermore, neurotrophins such as BDNF regulate the activity of endothelial nitric oxide synthase (eNOS). Thus, neurotrophins may be able to regulate PASM tone. Furthermore, ongoing studies suggest that neurotrophins influence cell proliferative pathways in PASM, and may thus play a role in pulmonary hypertension. Therefore, using cellular and molecualr techniques similar to those for the airway, we are exploring this novel aspect of PASM regulation.
- Caveolar Signaling. Caveolin isoforms are known to be expressed in PASM. Recent studies by other groups demonstrate that alterations in caveolin-1 expression influences the pathology and physiology of pulmonary hypertension. Using siRNA, overexpression vector, pulmonary hypertension animal models, and fluorescence confocal imaging technologies, we are currently exploring the role of caveolar components and interactions between signaling mechanisms in human PASM and their contribution to pulmonary hypertension.
