Therapeutic MK2 inhibition blocks pathological vascular smooth muscle cell phenotype switch

Tierney, J.W.; Evans, Brian C.; Cheung‐Flynn, Joyce; Wang, Bo; Colazo, Juan M.; Polcz, Monica; Cook, Rebecca S.; Brophy, Colleen M.; Duvall, Craig L.

doi:10.1172/jci.insight.142339

Cited by 12 publications

(14 citation statements)

References 57 publications

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“…As the fundamental formative and functional constituent of the arterial wall, vascular smooth muscle cells (VSMCs) play a role in maintaining vascular tone and integrity, adjusting the pressure in the lumen, distributing the blood volume, and contributing substantially to preserving vascular homeostasis [ 1 , 2 ]. In an internal homeostatic environment, highly differentiated VSMCs in the tunica media are spindle-shaped, express abundant contractile proteins (e.g., α-smooth muscle actin (α-SMA), calponin 1 (CNN1), smooth muscle myosin heavy chain (SMMHC), and smooth muscle protein 22-α(SM22α)), and undergo negligible proliferation and migration [ 3 , 4 , 5 ].…”

Section: Vascular Smooth Muscle Cellsmentioning

confidence: 99%

“…In healthy mature vessels, the intimal layer is composed mainly of endothelial cells, while the amount of contractile VSMCs in the intimal layer is negligible [ 4 ]. The arterial endothelium forms a monolayer of cells that covers the interior luminal side of vascular vessels and provides a barrier between blood and tissues.…”

Section: Cardiovascular Diseases Associated With Vsmcs Phenotypic Swi...mentioning

confidence: 99%

“…Intimal hyperplasia (INH) is a normal complication of artery remodeling following a vascular injury [ 4 , 50 , 52 ]. Unfortunately, the uncontrolled proliferation of VSMCs and the deposition of vast amounts of extracellular matrix (ECM) will lead to excessive intimal hyperplasia and the consequent narrowing of the lumen, ultimately causing associated vascular diseases such as hypertension and atherosclerosis [ 4 , 7 , 49 ]. It can also occur as a result of vascular surgery, resulting in vascular stenosis and the failure of revascularization operations or worsening of the initial condition [ 48 , 53 ].…”

Section: Cardiovascular Diseases Associated With Vsmcs Phenotypic Swi...mentioning

confidence: 99%

“…Percutaneous transluminal coronary angioplasty with balloon inflation applied to patients with coronary artery stenosis began to come into vogue in the late 1970s [ 54 ]. With the gradual maturity of percutaneous transluminal angioplasty (PTA), its clinical utilization rate has increased, but restenosis is accompanied by problems that limit its long-term efficacy [ 4 , 55 ]. Bare-metal stents then began to be phased into clinical practice.…”

Section: Cardiovascular Diseases Associated With Vsmcs Phenotypic Swi...mentioning

confidence: 99%

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Vascular Smooth Muscle Cells Phenotypic Switching in Cardiovascular Diseases

Tang

Chen

Zhang

et al. 2022

Cells

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Vascular smooth muscle cells (VSMCs), the major cell type in the arterial vessel wall, have a contractile phenotype that maintains the normal vessel structure and function under physiological conditions. In response to stress or vascular injury, contractile VSMCs can switch to a less differentiated state (synthetic phenotype) to acquire the proliferative, migratory, and synthetic capabilities for tissue reparation. Imbalances in VSMCs phenotypic switching can result in a variety of cardiovascular diseases, including atherosclerosis, in-stent restenosis, aortic aneurysms, and vascular calcification. It is very important to identify the molecular mechanisms regulating VSMCs phenotypic switching to prevent and treat cardiovascular diseases with high morbidity and mortality. However, the key molecular mechanisms and signaling pathways participating in VSMCs phenotypic switching have still not been fully elucidated despite long-term efforts by cardiovascular researchers. In this review, we provide an updated summary of the recent studies and systematic knowledge of VSMCs phenotypic switching in atherosclerosis, in-stent restenosis, aortic aneurysms, and vascular calcification, which may help guide future research and provide novel insights into the prevention and treatment of related diseases.

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Section: Vascular Smooth Muscle Cellsmentioning

confidence: 99%

Section: Cardiovascular Diseases Associated With Vsmcs Phenotypic Swi...mentioning

confidence: 99%

Section: Cardiovascular Diseases Associated With Vsmcs Phenotypic Swi...mentioning

confidence: 99%

Section: Cardiovascular Diseases Associated With Vsmcs Phenotypic Swi...mentioning

confidence: 99%

See 2 more Smart Citations

Vascular Smooth Muscle Cells Phenotypic Switching in Cardiovascular Diseases

Tang

Chen

Zhang

et al. 2022

Cells

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“…Synthetic VSMCs are prone to further differentiate into alternative phenotypes such as macrophage-like and osteogenic VSMCs. Although some scholars believe that there is no convincing marker for the synthetic VSMC, numerous studies have confirmed that osteopontin (OPN), MMP-9, epiregulin (EREG), and vimentin (VIM) are highly expressed in the synthetic VSMC [ 9 , 10 ]. A wide range of regulatory factors and signaling pathways are involved in the transition from contractile to synthetic VSMC, including metabolic factors, growth factors, non-coding RNA, immune-inflammatory molecules and so on.…”

Section: The Landscape Of Vsmcs Phenotypesmentioning

confidence: 99%

How vascular smooth muscle cell phenotype switching contributes to vascular disease

et al. 2022

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Vascular smooth muscle cells (VSMCs) are the most abundant cell in vessels. Earlier experiments have found that VSMCs possess high plasticity. Vascular injury stimulates VSMCs to switch into a dedifferentiated type, also known as synthetic VSMCs, with a high migration and proliferation capacity for repairing vascular injury. In recent years, largely owing to rapid technological advances in single-cell sequencing and cell-lineage tracing techniques, multiple VSMCs phenotypes have been uncovered in vascular aging, atherosclerosis (AS), aortic aneurysm (AA), etc. These VSMCs all down-regulate contractile proteins such as α-SMA and calponin1, and obtain specific markers and similar cellular functions of osteoblast, fibroblast, macrophage, and mesenchymal cells. This highly plastic phenotype transformation is regulated by a complex network consisting of circulating plasma substances, transcription factors, growth factors, inflammatory factors, non-coding RNAs, integrin family, and Notch pathway. This review focuses on phenotypic characteristics, molecular profile and the functional role of VSMCs phenotype landscape; the molecular mechanism regulating VSMCs phenotype switching; and the contribution of VSMCs phenotype switching to vascular aging, AS, and AA.

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Intravascular delivery of an MK2 inhibitory peptide to prevent restenosis after angioplasty

Tierney,

Francisco,

et al. 2025

Biomaterials

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Therapeutic MK2 inhibition blocks pathological vascular smooth muscle cell phenotype switch

Cited by 12 publications

References 57 publications

Vascular Smooth Muscle Cells Phenotypic Switching in Cardiovascular Diseases

Vascular Smooth Muscle Cells Phenotypic Switching in Cardiovascular Diseases

How vascular smooth muscle cell phenotype switching contributes to vascular disease

Intravascular delivery of an MK2 inhibitory peptide to prevent restenosis after angioplasty

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