Pulmonary vascular smooth muscle (PVSM)

Pulmonary vascular smooth muscle cells (PVSM), also known as pulmonary artery smooth muscle cells (PASMCs), form the medial layer of pulmonary arteries and regulate vascular tone through contraction and relaxation, primarily via calcium-dependent mechanisms and signaling pathways involving myosin light chain kinase (MLCK), phosphatase (MLCP), and Rho kinase. These cells respond to stimuli like thromboxane mimetics (U46619), prostaglandins (PGF2α), alpha-1 adrenergics, and endothelin, producing maximal tension comparable to potassium chloride depolarization. In pulmonary arterial hypertension (PAH), PVSM exhibit excessive proliferation, resistance to apoptosis, heightened stiffness, and remodeling, contributing to elevated pulmonary vascular resistance (PVR) and right heart strain. Therapeutic drugs target PVSM signaling to promote relaxation: PDE5 inhibitors (e.g., sildenafil) increase cGMP to soften cells and reduce stiffness, endothelin receptor antagonists (e.g., macitentan) block vasoconstrictive receptors, and sGC stimulators (e.g., riociguat) enhance NO-dependent pathways, with combination therapies showing additive effects on mechanical properties. PVSM interact with endothelial cells and adventitial fibroblasts via factors like endothelin-1, miR-143 exosomes, and extracellular matrix components, amplifying pathological remodeling in PAH. While not a single molecular entity, PVSM contractility is a central hub for PAH therapies, though advanced disease limits efficacy.

Other names

Pulmonary artery smooth muscle cells (PASMCs)pulmonary arterial smooth muscle cells

Decrease vasoconstriction via cGMP elevation (PDE5i like sildenafil), endothelin receptor blockade (ERAs like macitentan), sGC stimulation (riociguat), prostacyclin pathway activation (selexipag), Rho kinase inhibition