Diverse origin of intimal cells: Smooth muscle cells, myofibroblasts, fibroblasts, and beyond?

The formation of vascular lesions is invariably associated with the accumulation of mesenchymal cells and their products in the intima, which either compromise the vessel lumen or contribute to retention of atherogenic molecules (reviewed in References 1 and 2).1,2⇓ As a result, pathological intimal hyperplasia is pivotal in the development of a wide range of clinical conditions, which are associated with increased cardiovascular morbidity and mortality. Nonetheless, the origin of intimal cells has remained a controversial issue in vascular biology and clinical cardiology. In addition to the expansion of preexisting intimal cells, the initial hypothesis argued for phenotypic modulation of medial smooth muscle cells (SMCs) from a contractile to a synthetic phenotype (dedifferentiation), resulting in their migration into the intima.3,4⇓ Several recent investigations, however, have shed new light on the mechanisms of arterial remodeling, coronary restenosis after transcatheter interventions, and vein graft changes after arterialization, which are accompanied by marked alterations in cellular composition of the affected vessel. Understanding how the vasculature alters its composition holds the key to discerning vascular responses under physiological and pathological conditions (Figure 1). In a recent issue of Circulation Research , Hu and colleagues5 join this quest, focusing on the origin of intimal cells during vein graft remodeling. In contrast to numerous observations after arterial injury, there are relatively few studies of vein graft remodeling under dyslipidemic conditions, making the analysis of vein grafts in apoE-deficient mice clearly relevant. In different types of transgenic animals, the authors demonstrated that intima of venous isografts appeared to contain SMC-like cells originating from both donor and recipient, with no apparent contribution of bone marrow-derived cells. These findings suggest vascular-bed dependent differences in the mechanisms of repair and remodeling. They also underscore the diverse cellular origin of intimal hyperplasia, which may originate from …