Pre–B-cell Colony-Enhancing Factor Regulates Vascular Smooth Muscle Maturation Through a NAD + -Dependent Mechanism

Abstract

See related article, pages 25–34 There is a growing recognition of diversity in the morphology and function of vascular smooth muscle cells (SMCs). Diversity is both visible, with SMCs of different shape coexisting in arteries, and functional, manifest through differences in ionic profile, oxygen-sensitivity, proliferative capacity, and apoptosis susceptibility. SMC diversity is evident temporally (differences within a segment during development) and geographically (differences in SMCs between functionally discrete vascular segments within a single circulation).1 Moreover, many vibrant “vascular villages” display rich diversity within a single vascular segment, with heterogeneity in SMCs that exist side by side.2,3 The article by Pickering’s group addresses the molecular mechanism underlying a form of SMC diversity that has morphological and functional aspects; namely the existence of synthetic versus contractile SMCs.4 It is an important contribution because, in addressing their own hypothesis, they reveal a mechanism that has relevance to several unresolved questions in vascular biology.4 How do blood vessels regulate the transition from fetus to adult? What is the molecular basis for SMC diversity? How does acute redox regulation of vascular tone translate to altered vascular structure in hypertension? By providing partial answers to these questions, their work has implications for hypoxic pulmonary vasoconstriction (HPV),1,2 pulmonary hypertension,3 systemic hypertension, vascular repair, and atherosclerosis. The Pickering group used 2 clonal SMC lines, derived from human mammary arteries, to study the molecular mechanism for the maturational conversion from a proliferative to a constrictive phenotype. One cell line mimicked the SMC in fetal or healing arteries, being morphologically “Rubenesque” and possessed a synthetic noncontractile phenotype; the other line of cells was svelte, contractile, and thus, mature4 (Figure). Triggered by removal of serum, the synthetic, proliferating cells become elongate, spindle-shaped, and developed a contractile phenotype accompanied by apoptosis resistance. PBEF determines …