Some very serious diseases – aortic aneurysm, coronary artery atherosclerosis, and pulmonary hypertension, to name examples – involve pathological changes in the size and structure of the layers of smooth muscle that surround arteries. These smooth-muscle layers’ carefully coordinated contractility is essential to the regulation of blood flow.
But little is known about how the concentric layers of muscle cells and connective-tissue coating are laid down around the initial endothelial tubes that serve as starter materials for blood vessels. So it’s hard to know how to fix things when the process is dysregulated.
Mark Krasnow, PhD, who chairs Stanford’s biochemistry department, and his teammates have taken a big step toward solving that riddle by capturing some important details of how arterial walls are generated in the first place. In a just-out study, “Radial construction of an arterial wall,” published in Developmental Cell, Krasnow and his colleagues showed that the pulmonary artery wall (and probably many if not all other types of artery walls) is built up from the inside out, layer by layer.
This paving project is directed, in turn, by two separate but closely orchestrated processes: first, the induction of successive cell layers out of initally undifferentiated surrounding connective tissue called mesenchyme; and, second, a carefully programmed invasion of outer layers by outward-migrating cells from the inner layers, in response to chemical gradients that serve as guiding signals. Disruption of that pattern of chemical signals, then, may contribute (possibly in a big way) to pathological proliferation and pinching by arterial smooth muscle layers.
Coronary artery atherosclerosis alone is the biggest single killer of men and women in the United States, and pulmonary hypertension is particularly nasty. Understanding how to prevent either of those life-threatening disorders, or how to resolve them in the early stages, would be a major medical coup. Much like arterial walls, this understanding is built up layer by layer.