Neointimal hyperplasia

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Neointimal hyperplasia refers to proliferation and migration of vascular smooth muscle cells primarily in the tunica intima, resulting in the thickening of arterial walls and decreased arterial lumen space. [1] [2] Neointimal hyperplasia is the major cause of restenosis after percutaneous coronary interventions such as stenting or angioplasty. [1] The term neointima is used because the cells in the hyperplastic regions of the vascular wall have histological characteristics of both intima and normal artery cells. [2]

Contents

Causes

Neointimal hyperplasia first develops with damage to the arterial wall, followed by platelet aggregation at the site of injury, recruitment of inflammatory cells, proliferation and migration of vascular smooth muscle cells, and collagen deposition. [3]

Mechanical injury of arterials due to stretching of arterial walls with a balloon catheter results in the recruitment of cells such as monocytes, macrophages, and neutrophils to the site of injury. [4] [5] Macrophages in particular express many growth factors, cytokines, and enzymes that facilitate vascular smooth muscle cell migration and proliferation. [4]

C-reactive protein is a systemic inflammatory mediator correlated with neointimal hyperplasia, but it is still unknown if this protein is a marker of increased risk or a causative agent of the condition. [4]

Prevention

P radioactive β-emitting stents were used in coronary artery lesions with results showing inhibition of neointimal hyperplasia in a dose-dependent manner. [6] A 6-month follow up post-implantation of the radioactive stents showed little adverse side-effects in the patients. [6] However, more recent studies have shown that patients have a late progression of in-stent neointimal hyperplasia after 1 year of radioactive stent implantation, suggesting a delay in the development of neointimal hyperplasia rather than a prevention or decline of the condition. [7]

Drug-eluting stents coated with anti-proliferative chemicals are used to counteract neointimal hyperplasia after stents placement. [8] Drug-eluting stents that release resveratrol and quercetin show promise with marked reduction in intimal hyperplasia compared to bare, metal stents. [1]

Treatment

Anti-inflammatory treatment is effective in limiting the development of neointimal hyperplasia. [4] In rabbits, the use of IL-10 to reduce function of circulating monocytes and inhibition of leukocyte adhesion with antibodies reduced formation of neointimal hyperplasia after angioplasty and stenting. [4]

Nitric oxide-based treatment for the treatment of cardiovascular pathologies has shown promise in the treatment of neointimal hyperplasia. [3] However, the difficulty in controlled, local release of nitric oxide has limited its clinical use for neointimal hyperplasia. [3] Polymer-based perivascular wraps are attracting growing interest for their potential use to deliver nitric oxide and other drugs in the treatment of neointimal hyperplasia. [3]

Exendin-4, a glucagon-like peptide-1 receptor (GLP-1) agonist used as drug treatment for type 2 diabetes inhibits neointimal hyperplasia. [9] The use of PKA inhibitors reverses the inhibitory effects of exendin-4, suggesting that the anti-proliferative effects of exendin-4 involves the cAMP-PKA pathway. [9] Exendin-4 inhibits TNFα production by macrophages to reduce inflammation, which may play another role in inhibiting neointimal hyperplasia. [9]

See also

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Atherosclerosis form of arteriosclerosis

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Restenosis

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References

  1. 1 2 3 Kleinedler, James J; Foley, John D; Orchard, Elysse A; Dugas, Tammy R (2012). "Novel nanocomposite stent coating releasing resveratrol and quercetin reduces neointimal hyperplasia and promotes re-endothelialization". Journal of Controlled Release. 159 (1): 27–33. doi:10.1016/j.jconrel.2012.01.008. PMID   22269665.
  2. 1 2 Purcell, C; Tennant, M; McGeachie, J (1997). "Neo-intimal hyperplasia in vascular grafts and its implications for autologous arterial grafting". Annals of the Royal College of Surgeons of England. 79 (3): 164–8. PMC   2502879 . PMID   9196335.
  3. 1 2 3 4 Serrano, M. Concepcion; Vavra, Ashley K; Jen, Michele; Hogg, Melissa E; Murar, Jozef; Martinez, Janet; Keefer, Larry K; Ameer, Guillermo A; Kibbe, Melina R (2011). "Poly(diol-co-citrate)s as Novel Elastomeric Perivascular Wraps for the Reduction of Neointimal Hyperplasia". Macromolecular Bioscience. 11 (5): 700–9. doi:10.1002/mabi.201000509. PMC   4068126 . PMID   21341372.
  4. 1 2 3 4 5 Danenberg, H. D; Welt, F. G; Walker m, 3rd; Seifert, P; Toegel, G. S; Edelman, E. R (2002). "Systemic inflammation induced by lipopolysaccharide increases neointimal formation after balloon and stent injury in rabbits". Circulation. 105 (24): 2917–22. doi: 10.1161/01.cir.0000018168.15904.bb . PMID   12070123.
  5. ↑ Shah, P. K (2003). "Inflammation, Neointimal Hyperplasia, and Restenosis: As the Leukocytes Roll, the Arteries Thicken". Circulation. 107 (17): 2175–7. doi: 10.1161/01.CIR.0000069943.41206.BD . PMID   12732592.
  6. 1 2 Albiero, R; Adamian, M; Kobayashi, N; Amato, A; Vaghetti, M; Di Mario, C; Colombo, A (2000). "Short- and intermediate-term results of (32)P radioactive beta-emitting stent implantation in patients with coronary artery disease: The Milan Dose-Response Study". Circulation. 101 (1): 18–26. doi: 10.1161/01.cir.101.1.18 . PMID   10618299.
  7. ↑ Kay, I. P; Wardeh, A. J; Kozuma, K; Foley, D. P; Knook, A. H. M; Thury, A; Sianos, G; Van Der Giessen, W. J; Levendag, P. C; Serruys, P. W (2001). "Radioactive Stents Delay but Do Not Prevent In-Stent Neointimal Hyperplasia". Circulation. 103 (1): 14–7. doi: 10.1161/01.CIR.103.1.14 . PMID   11136678.
  8. ↑ Wang, Dongdong; Uhrin, Pavel; Mocan, Andrei; Waltenberger, Birgit; Breuss, Johannes M; Tewari, Devesh; Mihaly-Bison, Judit; Huminiecki, Łukasz; Starzyński, Rafał R; Tzvetkov, Nikolay T; Horbańczuk, Jarosław; Atanasov, Atanas G (2018). "Vascular smooth muscle cell proliferation as a therapeutic target. Part 1: Molecular targets and pathways". Biotechnology Advances. 36 (6): 1586–1607. doi:10.1016/j.biotechadv.2018.04.006. PMID   29684502.
  9. 1 2 3 Hirata, Yoichiro; Kurobe, Hirotsugu; Nishio, Chika; Tanaka, Kimie; Fukuda, Daiju; Uematsu, Etsuko; Nishimoto, Sachiko; Soeki, Takeshi; Harada, Nagakatsu; Sakaue, Hiroshi; Kitagawa, Tetsuya; Shimabukuro, Michio; Nakaya, Yutaka; Sata, Masataka (2013). "Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates neointimal hyperplasia after vascular injury". European Journal of Pharmacology. 699 (1–3): 106–11. doi:10.1016/j.ejphar.2012.11.057. PMID   23220706.
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