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Human aortic smooth muscle cells

Smooth Muscle Cells: Contractile Controllers

 

Smooth muscle cells are located in many organs throughout the body, most notably in the vasculature, but also in the bladder, uterus, and gastrointestinal system. They regulate contraction in these organs, and are of particular importance in blood vessels. Here, they regulate blood pressure and mediate vessel integrity and homeostasis. When they become dysregulated, they can contribute to the pathogenesis of vascular diseases, such as atherosclerosis. Vascular SMCs have significant phenotypic plasticity and as such, can exhibit multiple phenotypes. The phenomenon known as phenotypic switching occurs during the development of atherosclerosis, and refers to the process by which vascular SMCs acquire a “synthetic” phenotype, characterized by dedifferentiation from a contractile phenotype.

Recent Studies Featuring Lifeline® SMCs

Myoendothelial gap junctions provide a critical link between vascular smooth muscle cells and endothelial calls. In a study this year, Zhang et al. investigated the role of myoendothelial gap junctions on phenotypic switching of SMCs and how laminar shear stress affects this process. They set up a co-culture system using Lifeline® human coronary artery smooth muscle cells (HCASMCs) and human coronary artery endothelial cells (HCAECs). They found that HCASMCs and HCAECs formed myoendothelial gap junctions that expressed connexin 40 (CX40) and CX43. However, when exposed to laminar shear stress of 5 dyn/cm3, but not 12 dyn/cm3, SMCs began to undergo a phenotypic switch to the synthetic phenotype. This was accompanied by a connexin switch within myoendothelial gap junctions, from CX40-CX43 junctions to CX43-CX43 junctions. In accordance with reported characteristics of SMC phenotypic switching, the researchers observed an increase in platelet-derived growth factor (PDGF) signaling. Together, the results of this study suggest that laminar shear stress of 5 dyn/cm3 can alter myoendothelial gap junctions and induce SMC phenotypic switching, which may be associated with a pro-atherosclerotic effect.

Restenosis following surgical intervention for peripheral artery disease is a significant problem that may benefit from siRNA-mediated therapy. While potentially useful, this type of therapy presents a number of challenges that stem from siRNA delivery and efficiency. To determine whether better delivery systems could be developed using biodegradable polymers, Bools et al. investigated the feasibility of poly(B-amino ester) (PBAE) and polyethylenimine (PEI) as siRNA delivery agents. The researchers used Lifeline® human aortic smooth muscle cells to test the two polymer siRNA delivery agents to target GAPDH, a housekeeping gene. They found that while PBAE and PEI achieved similar knockdown efficiency, PEI-mediated knockdown required higher conjugate concentration and had greater cytotoxicity. The researchers showed, however, that shorter exposure to PEI yielded the same silencing efficiency, but decreased the cytotoxic effect. Therefore, the researchers concluded that both PBAE and PEI are useful polymer agents that can be explored for delivery of siRNAs in the clinic.

Lifeline Normal Human Smooth Muscle Cells and Optimized Culture Medium

Lifeline® SMCs are available from various organ sites and optimized for culture in VascuLife SMC® medium. They include:

Are you using Lifeline® cells in your research? Let us know how you are using Lifeline® cells to answer your scientific questions and your study could be featured here on our blog!

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