Vascular Smooth Muscle Cells: Regulators of Blood Vessel Function

Smooth muscle cells (SMCs) are present in most contractile organs, including the bladder, gastrointestinal tract, and blood vessels. Smooth muscle cells in blood vessels are termed vascular smooth muscle cells (VSMCs), and are responsible for maintaining blood pressure and vessel homeostasis. VSMCs have the potential to migrate and do so in response to vessel injury. VSMC migration is initiated upon certain stimulatory signals, one of which includes platelet-derived growth factor (PDGF), which is released upon vessel injury. PDGF binds to its receptor (PDGFR) on VSMCs, and initiates a signaling cascade that culminates in cytoskeletal rearrangements and cell migration.

VSMC dysfunction is implicated in a number of vascular conditions, most notably atherosclerosis. VSMCs also contribute to intimal hyperplasia, a condition that occurs in response to vessel injury, often following a vascular procedure. Intimal hyperplasia occurs when VSMCs migrate to the site of injury and proliferate, causing thickening of the vessel intima (the innermost layer of a blood vessel), which decreases the luminal space. The two studies described below use Lifeline® VSMCs to investigate the molecular mechanism of and therapeutic intervention for intimal hyperplasia.

Recent Studies Using Lifeline® Smooth Muscle Cells

Treatment of initimal hyperplasia has often made use of anti-proliferative drugs that interfere with VSMC proliferation and migration. However, these same drugs can also affect the proliferation of endothelial cells, which may partially cause late stent thrombosis. Therefore, there is a need for therapeutics that are selective for VSMCs. In a 2016 study, Thiel et al. investigated the selectivity and efficacy of RNA aptamers for treatment of intimal hyperplasia. RNA aptamers are RNA molecules that bind to targets with high affinity in a structure/sequence-dependent manner. Using Lifeline® Aortic Smooth Muscle Cells as their VSMC model, the researchers identified one aptamer (termed aptamer 14, or Apt 14) that was specific for human VSMCs. Apt 14 inhibited VSMC migration in response to multiple VSMC migratory stimulants, including PDGF.

Importantly, Apt 14 had no effect on Lifeline® vascular endothelial cells. Furthermore, in rats with carotid artery injury, Apt 14 treatment decreased development of neointima, suggesting that it is effective in vivo. To determine the mechanism by which Apt 14 affects VSMCs, the researchers investigated PDGFR-b as a candidate target. They found that Apt 14 binds PDGFR-b and blocks its phosphorylation, as well as activation of its downstream effectors. Finally, the group demonstrated that Apt 14 was stable in human serum and not cytotoxic. Together, their results suggest that Apt 14 is an anti-migratory agent that is selective for VSMCs and safe for use in humans.

Androgen deficiency in males can contribute to vascular disease, but the mechanism by which it affects intimal hyperplasia is unknown. In a new study, Freeman and colleagues set out to determine how androgen deficiency contributes to intimal hyperplasia and how hormone replacement affects VSMCs. Using a rat model of vascular injury, combined with orchiectomy (surgical testicle removal), the research group found that compared to intact male animals, intimal hyperplasia increased in orchiectomized rats. Importantly, intimal hyperplasia improved with high doses of hormone replacement (5 mg testosterone). Interestingly, the urotensin II receptor (UTSR) was increased in testosterone-treated injured vascular tissue.

Although urotensin II stimulates VSMC proliferation, the researchers found that exogenous testosterone treatment of Lifeline® Aortic Smooth Muscle Cells did not affect gene expression of proliferative markers. Finally, the group demonstrated that testosterone treatment of Lifeline® aortic SMCs also decreased the cellular pool of filamentous actin, compared to free actin (F:G actin ratio), suggesting that this treatment induces cytoskeletal rearrangement and may affect vasoconstriction. Together, the results of this study demonstrate that androgen deficiency contributes to intimal hyperplasia, which may be attenuated by hormone replacement. However, the hormone replacement in this context results in upregulation of UTSR and cytoskeletal rearrangements that are incompletely understood, and may be deleterious to proper VSMC vasoconstriction.

Lifeline Smooth Muscle Cells

Lifeline® provides normal human smooth muscle cells from multiple cell types, including:

• Bronchial/Tracheal Smooth Muscle Cells
• Lung Smooth Muscle Cells
• Aortic Smooth Muscle Cells
• Bladder Smooth Muscle Cells
• Coronary Artery Smooth Muscle Cells
• Pulmonary Artery Smooth Muscle Cells
• Uterine Smooth Muscle Cells

Let us know how you are using Lifeline® cells for your research needs and your study could be featured here on our blog!