Smooth Muscle in Health and Disease

Smooth muscle is dispersed throughout all organ systems where it imparts structure and also plays a role in repair and inflammation. However, the primary role of smooth muscle is contractile function and abnormalities in smooth muscle contractility and reactivity are pathogenic for diseases of every organ system. Smooth muscle dysfunction forms the molecular basis of many common diseases including those of the cardiovascular system (systemic and pulmonary hypertension as well as heart failure), the respiratory system (asthma and COPD), the gastrointestinal system (gastrointestinal dysmotility and inflammatory bowel diseases), as well as the genito-urinary system (impotence, genito-urinary and bladder dysfunction as well as uterine dysfunction and the associated disorders of pregnancy). A great deal has been learned about smooth muscle contractile function and dysfunction over the past few decades. Further, recent experiments using lineage and clonality tracing as well as single-cell RNA sequencing have demonstrated the existence of significant phenotypic diversity of smooth muscle in both the normal and pathological state, as well as the mechanism controlling these phenotypic transitions. Nonetheless, therapeutic approaches to disorders of the function of smooth muscle have been relatively stagnant. This suggests an opportunity to target specific defects in smooth muscle contractility and reactivity in specific diseases, so-called personalized precision medicine. This series will review recent findings on the molecular basis of smooth muscle contractility and also focus on some of the newer findings in this field including genetic basis for smooth muscle dysfunction in common diseases, modeling smooth muscle dysfunction with human stem cells (“disease-in-a-dish”), new insights into novel signaling pathways in disease pathogenesis, and new therapeutic modalities, both small chemicals and genetic engineering.