Pharmacological prevention of intimal hyperplasia: A state-of-the-art review

Melnik, Tamara; Jordan, Olivier; Corpataux, Jean-Marc; Delié, Florence; Saucy, François

doi:10.1016/j.pharmthera.2022.108157

Cited by 34 publications

(22 citation statements)

References 104 publications

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“…The dose that can be administered systemically is limited due to side effects, and may not provide the required amount of the active pharmacological ingredient at the injury site, resulting in up to 40% of vein graft failure [ 2 ]. Perivascular administration, locally at the adventitia has been efficient to inhibit IH, with promising results observed with application of statins or anti-inflammatory drugs [ 3 , 4 , 5 ], reviewed in [ 6 ]. To date, there are no clinically approved formulations for targeted local perivascular prevention of graft failure after bypass surgery [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Bioadhesive Hyaluronic Acid/Dopamine Hydrogels for Vascular Applications Prepared by Initiator-Free Crosslinking

Melnik

Ameur

Kanfar

et al. 2022

IJMS

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Intimal hyperplasia, a vascular pathology characterized by vessel wall thickening, is implicated in vein graft failures. For efficient prevention, a biodegradable drug delivery system should be applied externally to the graft for an extended time. Finding a gel suitable for such a system is challenging. We have synthesized HA-Dopamine conjugates (HA-Dop) with several degrees of substitution (DS) and used two crosslinking methods: initiator-free crosslinking by basic pH shift or commonly used crosslinking by a strong oxidizer, sodium periodate. The rheological properties, bioadhesion to vascular tissue, cytocompatibility with fibroblasts have been compared for both methods. Our results suggest that initiator-free crosslinking provides HA-Dop gels with more adequate properties with regards to vascular application than crosslinking by strong oxidizer. We have also established the cytocompatibility of the initiator-free crosslinked HA-Dop gels and the cytotoxicity of dopamine-sodium periodate combinations. Furthermore, we have incorporated a drug with anti-restenotic effect in perivascular application, atorvastatin, into the gel, which showed adequate release profile for intimal hyperplasia prevention. The oxidizer-free formulation with improved bioadhesion holds promise as an efficient and safe drug delivery system for vascular applications.

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Section: Introductionmentioning

confidence: 99%

Bioadhesive Hyaluronic Acid/Dopamine Hydrogels for Vascular Applications Prepared by Initiator-Free Crosslinking

Melnik

Ameur

Kanfar

et al. 2022

IJMS

Self Cite

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“…Proliferation and migration of VSMCs in the arterial wall are two critical pathological processes in the development of neointimal hyperplasia underlying obstructive vascular diseases, such as atherosclerosis and restenosis after percutaneous transluminal coronary angioplasty [ 35 ]. We found that VSMC-specific deletion of EP4 remarkably suppressed, while VSMC-selective overexpression of EP4 exaggerated, the PCNA positive cells in the vascular neointima, suggesting that VSMC EP4 may promote neointimal hyperplasia via enhancing VSMC proliferation.…”

Section: Discussionmentioning

confidence: 99%

The Prostaglandin E2 Receptor EP4 Promotes Vascular Neointimal Hyperplasia through Translational Control of Tenascin C via the cAMP/PKA/mTORC1/rpS6 Pathway

Fang

Bao

et al. 2022

Cells

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Prostaglandin E2 (PGE2) is an important metabolite of arachidonic acid which plays a crucial role in vascular physiology and pathophysiology via its four receptors (EP1-4). However, the role of vascular smooth muscle cell (VSMC) EP4 in neointimal hyperplasia is largely unknown. Here we showed that VSMC-specific deletion of EP4 (VSMC-EP4) ameliorated, while VSMC-specific overexpression of human EP4 promoted, neointimal hyperplasia in mice subjected to femoral artery wire injury or carotid artery ligation. In vitro studies revealed that pharmacological activation of EP4 promoted, whereas inhibition of EP4 suppressed, proliferation and migration of primary-cultured VSMCs. Mechanically, EP4 significantly increased the protein expression of tenascin C (TN-C), a pro-proliferative and pro-migratory extracellular matrix protein, at the translational level. Knockdown of TN-C markedly suppressed EP4 agonist-induced VSMC proliferation and migration. Further studies uncovered that EP4 upregulated TN-C protein expression via the PKA/mTORC1/Ribosomal protein S6 (rpS6) pathway. Together, our findings demonstrate that VSMC EP4 increases TN-C protein expression to promote neointimal hyperplasia via the PKA-mTORC1-rpS6 pathway. Therefore, VSMC EP4 may represent a potential therapeutic target for vascular restenosis.

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“…In atherosclerosis, VSMCs migrate from the media into the intima and proliferate with the induction of platelet-derived growth factors [ 11 ]. Intimal hyperplasia is a severe consequence of VSMC proliferation, leading to luminal stenosis and endangering patients undergoing revascularization [ 20 ]. The abnormal status of VSMCs is tightly related to vascular growth factors, vasoactive substances, hemodynamics, oxidative stress and inflammatory factors [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Homeostasis in VSMCs as a Central Hub in Vascular Remodeling

Xia

Zhang

et al. 2023

IJMS

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Vascular remodeling is a common pathological hallmark of many cardiovascular diseases. Vascular smooth muscle cells (VSMCs) are the predominant cell type lining the tunica media and play a crucial role in maintaining aortic morphology, integrity, contraction and elasticity. Their abnormal proliferation, migration, apoptosis and other activities are tightly associated with a spectrum of structural and functional alterations in blood vessels. Emerging evidence suggests that mitochondria, the energy center of VSMCs, participate in vascular remodeling through multiple mechanisms. For example, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)-mediated mitochondrial biogenesis prevents VSMCs from proliferation and senescence. The imbalance between mitochondrial fusion and fission controls the abnormal proliferation, migration and phenotypic transformation of VSMCs. Guanosine triphosphate-hydrolyzing enzymes, including mitofusin 1 (MFN1), mitofusin 2 (MFN2), optic atrophy protein 1 (OPA1) and dynamin-related protein 1 (DRP1), are crucial for mitochondrial fusion and fission. In addition, abnormal mitophagy accelerates the senescence and apoptosis of VSMCs. PINK/Parkin and NIX/BINP3 pathways alleviate vascular remodeling by awakening mitophagy in VSMCs. Mitochondrial DNA (mtDNA) damage destroys the respiratory chain of VSMCs, resulting in excessive ROS production and decreased ATP levels, which are related to the proliferation, migration and apoptosis of VSMCs. Thus, maintaining mitochondrial homeostasis in VSMCs is a possible way to relieve pathologic vascular remodeling. This review aims to provide an overview of the role of mitochondria homeostasis in VSMCs during vascular remodeling and potential mitochondria-targeted therapies.

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Pharmacological prevention of intimal hyperplasia: A state-of-the-art review

Cited by 34 publications

References 104 publications

Bioadhesive Hyaluronic Acid/Dopamine Hydrogels for Vascular Applications Prepared by Initiator-Free Crosslinking

Bioadhesive Hyaluronic Acid/Dopamine Hydrogels for Vascular Applications Prepared by Initiator-Free Crosslinking

The Prostaglandin E2 Receptor EP4 Promotes Vascular Neointimal Hyperplasia through Translational Control of Tenascin C via the cAMP/PKA/mTORC1/rpS6 Pathway

Mitochondrial Homeostasis in VSMCs as a Central Hub in Vascular Remodeling

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