Smooth muscle cells from the anastomosed artery are the major precursors for neointima formation in both artery and vein grafts

Abstract

Accumulation of smooth muscle cells (SMC) results in neointima formation in injured vessels. Two graft models consisting of vein and artery grafts were created by anastomosing common carotid arteries to donor vessels. To identify the origin of the neointima cells from anastomosed arteries, we use Wnt1-Cre/reporter mice to label and track SMCs in the common carotid artery. The contribution of SMCs in the neighboring arteries to neointima formation was studied. On evaluating the artery grafts after 1 month, >90 % of the labeled neointima cells were found to have originated from the anastomosing host arteries. Most of the neointima cells were also smooth muscle α-actin positive (SMA-α+) and expressed the smooth muscle myosin heavy chain (SMMHC), the SMC terminal differentiation marker. In vein grafts, about 60 % SMA-α-positive cells were from anastomosing arteries. Bone marrow cells did not contribute to neointima SMCs in vein grafts, but did co-stain with markers of inflammatory cells. Wnt1 expression was not detected in the neointima cells in the vein or artery grafts, or the injured femoral arteries. Neointima SMCs showed the synthetic phenotype and were positively labeled with BrdU in vitro and in vivo. Treatment with the IGF-1 receptor inhibitor suppressed SMC proliferation and neointima formation in vein grafts. Our results indicate that SMCs from the neighboring artery are predominantly present in the neointima formed in both vein and artery grafts and that Wnt1-Cre mice can be used to explore the role of SMCs originating from neighboring vessels in vascular remodeling.

Axl modulates immune activation of smooth muscle cells in vein graft remodeling

“…However, in the present study, systemic deletion of Axl reduced intima thickness due to an increase in apoptosis in vein graft remodeling. These data suggest that the survival of immune cells in a more severe immunological model of vein graft remodeling is crucial compared with responses to low (20). It has been previously reported that higher doses of IFN-␥ could induce SMC death (7,25).…”

Long noncoding RNA NEAT1 (nuclear paraspeckle assembly transcript 1) is critical for phenotypic switching of vascular smooth muscle cells

“…Many occlusive vascular diseases in humans, including intimal hyperplasia after angioplasty, atherosclerosis, and restenosis following vascular interventions, are largely dependent upon VSMC phenotype modulation, contributing to progression of intimal lesions that compromise vessel patency (1,2). Although many studies have shown that, following arterial injury and in atherosclerosis neointima, VSMCs mostly originate from the local vessel wall (3)(4)(5)(6)(7)(8)(9)(10), there remains a lack of knowledge of the factors that can control the switch of SM phenotype in vascular diseases.…”

Hypoxia Differentially Regulates Arterial and Venous Smooth Muscle Cell Migration

“…These SMC acquire a pathological (proliferative and synthetic) phenotype in IH. Source of these abnormal SMC (host artery, circulating progenitor cells) is not completely understood [ 23 , 24 ]. In the present study we investigated the differences in migration behavior between venous and arterial derived SMC in response to hypoxia.…”