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Neointimal hyperplasia
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<h2 id="causes">Causes</h2> <p>Neointimal hyperplasia first develops with damage to the arterial wall, followed by <a href="/facts/Platelet_aggregation/I0xrDVGa">platelet aggregation</a> at the site of injury, recruitment of <a href="/facts/Inflammatory_cell/vsDunUK0">inflammatory cells</a>, proliferation and migration of vascular smooth muscle cells, and <a href="/facts/Collagen/KsyAb72K">collagen</a> deposition.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> </p><p>Mechanical injury of arterials due to stretching of arterial walls with a <a href="/facts/Balloon_catheter/H7nwK0g1">balloon catheter</a> results in the recruitment of cells such as monocytes, <a href="/facts/Macrophage/z7hkQu3o">macrophages</a>, and <a href="/facts/Neutrophil/KL6oTt8b">neutrophils</a> to the site of injury.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a><a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> Macrophages in particular express many growth factors, cytokines, and enzymes that facilitate vascular smooth muscle cell migration and proliferation.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> </p><p>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.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> </p> <h2 id="prevention">Prevention</h2> <p>P radioactive β-emitting stents were used in <a href="/facts/Coronary_artery/Xsx1dekd">coronary artery</a> lesions with results showing inhibition of neointimal hyperplasia in a dose-dependent manner.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> A 6-month follow up post-implantation of the radioactive stents showed little adverse side-effects in the patients.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> 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.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> </p><p><a href="/facts/Drug-eluting_stents/IGlK5API">Drug-eluting stents</a> coated with anti-proliferative chemicals are used to counteract neointimal hyperplasia after stents placement.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> Drug-eluting stents that release <a href="/facts/Resveratrol/5sF3fvl7">resveratrol</a> and <a href="/facts/Quercetin/Ed1BP1YD">quercetin</a> show promise with marked reduction in intimal hyperplasia compared to bare, metal stents.<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> </p> <h2 id="treatment">Treatment</h2> <p><a href="/facts/Anti-inflammatory/W27poSUd">Anti-inflammatory</a> treatment is effective in limiting the development of neointimal hyperplasia.<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> In rabbits, the use of <a href="/facts/Interleukin_10/f02nlvSu">IL-10</a> to reduce function of circulating <a href="/facts/Monocyte/FW4NNMKM">monocytes</a> and inhibition of <a href="/facts/Leukocyte/vsDunUK0">leukocyte</a> adhesion with <a href="/facts/Antibodies/MX8pdTdP">antibodies</a> reduced formation of neointimal hyperplasia after angioplasty and stenting.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> </p><p>Nitric oxide-based treatment for the treatment of cardiovascular pathologies has shown promise in the treatment of neointimal hyperplasia.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> However, the difficulty in controlled, local release of nitric oxide has limited its clinical use for neointimal hyperplasia.<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> 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.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> </p><p>Exendin-4, a <a href="/facts/Glucagon-like_peptide-1_receptor/HhqMt2wy">glucagon-like peptide-1 receptor</a> (GLP-1) agonist used as drug treatment for <a href="/facts/Type_2_diabetes/zCMXksmt">type 2 diabetes</a> inhibits neointimal hyperplasia.<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> The use of PKA inhibitors reverses the inhibitory effects of exendin-4, suggesting that the anti-proliferative effects of exendin-4 involves the <a href="/facts/Cyclic_adenosine_monophosphate/flK2vwUe">cAMP</a>-<a href="/facts/Protein_kinase_A/kaKoYfbp">PKA</a> pathway.<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> Exendin-4 inhibits TNFα production by macrophages to reduce inflammation, which may play another role in inhibiting neointimal hyperplasia.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Angioplasty/j2ausFmb">Angioplasty</a></li> <li><a href="/facts/Drug-eluting_stent/IGlK5API">Drug-eluting stent</a></li> <li><a href="/facts/Restenosis/cKNYGX9z">Restenosis</a></li> <li><a href="/facts/Stent/h8Ss3zlE">Stent</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2502879" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2502879</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2502879" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2502879</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068126" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068126</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>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.{{cite journal}}: CS1 maint: numeric names: authors list (link) <a href="http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12070123" target="_blank">http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12070123</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>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. <a href="https://doi.org/10.1161%2F01.CIR.0000069943.41206.BD" target="_blank">https://doi.org/10.1161%2F01.CIR.0000069943.41206.BD</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>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.{{cite journal}}: CS1 maint: numeric names: authors list (link) <a href="http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12070123" target="_blank">http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12070123</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>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.{{cite journal}}: CS1 maint: numeric names: authors list (link) <a href="http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12070123" target="_blank">http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12070123</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>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. <a href="http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10618299" target="_blank">http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10618299</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>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. <a href="http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10618299" target="_blank">http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10618299</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>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. hdl:1765/9562. PMID 11136678. <a href="https://doi.org/10.1161%2F01.CIR.103.1.14" target="_blank">https://doi.org/10.1161%2F01.CIR.103.1.14</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>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.{{cite journal}}: CS1 maint: numeric names: authors list (link) <a href="http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12070123" target="_blank">http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12070123</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>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.{{cite journal}}: CS1 maint: numeric names: authors list (link) <a href="http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12070123" target="_blank">http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12070123</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068126" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068126</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> <li id="fn:18"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068126" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068126</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></p></li> <li id="fn:19"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068126" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068126</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></p></li> <li id="fn:20"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></p></li> <li id="fn:21"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:21" class="footnote-back-ref">↩</a></p></li> <li id="fn:22"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:22" class="footnote-back-ref">↩</a></p></li> </ol>