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Vascular Smooth Muscle Cells in Arterial Pathologies
Vascular smooth muscle cells (VSMCs) play important physiological and pathophysiological roles. Two articles in the current issue focus on the latter in atherosclerosis1 and in pulmonary arterial hypertension (PAH).2 Notably, Allahverdian et al1 report that, in human coronary artery atherosclerotic plaques, many cells typically classified as macrophages are likely to be of VSMC origin, and Ricard et al2 report that, in PAH, VSMCs contributing to obstructive remodeling of the distal branches of the pulmonary artery likely arose from pericytes.
Article see p 1551 and p 1586
Although studies of macrophages in atherosclerosis far outnumber those of VSMCs, there is nonetheless a trove of data, including from humans, going back more than 50 years that clearly support an important role for VSMCs in both acute and chronic pathologies of the vessel wall (eg, see References 3–5). Of particular relevance to the 2 articles under discussion is the concept of VSMC phenotypic plasticity, which has support from classic ultrastructural studies5 and more recent lineage tracing experiments.6 Although the latter studies support the phenomenon of VSMC phenotypic plasticity, they have been limited to experimental animal model systems that may not faithfully recapitulate all aspects of human pathology. Indeed, atherosclerosis in coronary or cerebral arteries is rarely examined in mice, whereas these sites are of great interest in studies of the human disease. Thus, whether human VSMCs undergo phenotypic conversions in the context of atherosclerosis remains an unanswered question.
Now, as alluded to above, in this issue of Circulation, Allahverdian et al1 provide evidence for the phenotypic conversion of VSMCs of the coronary artery to a macrophage-like state during human atherogenesis.1 Through special fixation of the coronary vessels from explanted hearts, the authors were able to preserve intracellular lipid deposition and, by using …