Macrophages and Neovascularization in In-Stent Neoatherosclerosis: An Accelerated Inflammatory Phenotype by OCT with Therapeutic Implications

Keywords:
Coronary Restenosis; Phenotype/inflammation; Percutaneous Coronary Intervention; Atherosclerosis; Diagnostic, Imaging/methods

In this edition of Arquivos Brasileiros de Cardiologia, Pinheiro et al.¹ show optical coherence tomography (OCT) data with clear differences in inflammation and neovascularization among de novo atherosclerosis, in-stent restenosis due to intimal hyperplasia, and in-stent neoatherosclerosis.

Patients undergoing percutaneous coronary intervention with stent implantation may have recurrent symptoms of coronary heart disease due to in-stent restenosis due to vascular injury that triggers an intimal proliferative response,² minimized by current techniques and stents of new generation.³ However, the neointimal lesion secondary to a delay in neoendothelialization can lead to symptom recurrence, usually during the first year of coronary intervention.⁴

In patients with acute coronary syndromes, pronounced inflammatory responses can be detected for weeks,⁵ contributing to plaque instability⁶ and infarcted mass and ventricular remodeling after myocardial infarction.⁷ In addition, stent implantation also promotes systemic and local inflammation.⁸

Russel Ross⁹ defined atherosclerosis as an inflammatory disease.⁹ Pinheiro et al.¹ reported increased inflammatory activity and neovascularization among de novo lesions and intra-stent neoatherosclerosis. These two forms of atherosclerosis may have important differences in pathophysiology. Atherosclerosis in native arteries is related to cardiovascular risk factors, and it takes a long time to develop, but after acute coronary syndromes and/or stent implantation, systemic inflammation may accelerate its progression.⁶ Intra-stent neoatherosclerosis is a new and fast form of atherosclerosis-related to vascular injury and inflammation.⁴

Complications such as atherosclerotic plaque rupture seem to be associated not only with plaque expansion¹⁰ but also with characteristics of greater vulnerability (inflammatory content, thin fibrous cap, and higher lipid content).¹¹ OCT has properly addressed all these aspects. The article’s findings have important implications:

The need for appropriate therapy (including highly-effective lipid-lowering therapies) to prevent the development of atherosclerosis in native coronary arteries and possibly in the intra-stent atherosclerosis.¹²,¹³

The study raises the debate about the relevance of residual inflammatory risk and the opportunity to use anti-inflammatory drugs.¹⁴,¹⁵

More studies are necessary to understand better intra-stent neoatherosclerosis and the need for more comprehensive strategies, to prevent this form of stent failure.

• Short Editorial related to the article: Inflammatory Phenotype by OCT Coronary Imaging: Specific Features Among De Novo Lesions, In-Stent Neointima, and In-Stent Neo-Atherosclerosis

Referências

• ¹
  Pinheiro LFM, Carzon S, Mariani Jr J, Prado CFA, Caixeta AM, Almeida BO, Lemos PA. Inflammatory Phenotype by OCT Coronary Imaging: Specific Features Among De Novo Lesions, In-Stent Neointima, and In-Stent Neo-Atherosclerosis. Arq Bras Cardiol. 2022; 119(6):931-937.
• ²
  Fonseca FA, Izar MC, Fuster V, Gallo R, Padurean A, Fallon FT, et al. Chronic endothelial dysfunction after oversized coronary balloon angioplasty in pigs:a 12-week follow-up of coronary reactivity in vivo and in vitro.Atherosclerosis 2001;154(1):61-9. DOI: 10.1016/s0021-9150(00)00458-5
  » https://doi.org/10.1016/s0021-9150(00)00458-5
• ³
  Park SJ, Kang SJ, Virmani R, Nakano M, Ueda Y. In-stent neoatherosclerosis: a final common pathway of late stent failure. J Am Coll Cardiol. 2012;59(23):2051-7. DOI: 10.1016/j.jacc.2011.10.909
  » https://doi.org/10.1016/j.jacc.2011.10.909
• ⁴
  Giustino G, Colombo A, Camaj A, Yasumura K, Mehran R, Stone GW, et al. Coronary In-Stent Restenosis: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022;80(4):348-72. DOI: 10.1016/j.jacc.2022.05.017
  » https://doi.org/10.1016/j.jacc.2022.05.017
• ⁵
  Hilgendorf I, Gerhardt LM, Tan TC, Winter C, Holderried TA, Chousterman BG, et al. Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium. Circ Res. 2014;114(10):1611-22. DOI: 10.1161/CIRCRESAHA.114.303204
  » https://doi.org/10.1161/CIRCRESAHA.114.303204
• ⁶
  Dutta P, Courties G, Wei Y, Leuschner F, Gorbatov R, Robbins CS, et al. Myocardial infarction accelerates atherosclerosis. Nature. 2012;487(7407)325-9. DOI: 10.1038/nature11260
  » https://doi.org/10.1038/nature11260
• ⁷
  Fonseca FA, Izar MC. Role of Inflammation in Cardiac Remodeling After Acute Myocardial Infarction. Front Physiol. 2022;13:927163. DOI: 10.3389/fphys.2022.927163
  » https://doi.org/10.3389/fphys.2022.927163
• ⁸
  Farsky PS, Hirata MH, Arnoni RT, Almeida AFS, Issa M, Lima PHO. Persistent Inflammatory Activity in Blood Cells and Artery Tissue from Patients with Previous Bare Metal Stent. Arq Bras Cardiol. 2018;111(2):134–41. DOI: 10.5935/abc.20180119
  » https://doi.org/10.5935/abc.20180119
• ⁹
  Ross R. Atherosclerosis - an inflammatory disease. N Engl J Med. 1999;340(2):115-26. DOI: 10.1056/NEJM199901143400207
  » https://doi.org/10.1056/NEJM199901143400207
• ¹⁰
  Ahmadi A, Argulian E, Leipsic J, Newby DE, Narula J. From Subclinical Atherosclerosis to Plaque Progression and Acute Coronary Events: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;74(12):1608-17. DOI: 10.1016/j.jacc.2019.08.012
  » https://doi.org/10.1016/j.jacc.2019.08.012
• ¹¹
  Dawson LP, Lum M, Nerleker N, Nicholls SJ, Layland J. Coronary Atherosclerotic Plaque Regression: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022 Jan 4;79(1):66-82. DOI: 10.1016/j.jacc.2021.10.035
  » https://doi.org/10.1016/j.jacc.2021.10.035
• ¹²
  Nicholls SJ, Kataoka Y, Nissen SE, Prati F, Windecker S, Puri R, et al. Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction. JACC Cardiovasc Imaging. 2022;15(7):1308-21. DOI: 10.1016/j.jcmg.2022.03.002
  » https://doi.org/10.1016/j.jcmg.2022.03.002
• ¹³
  Räber L, Ueki Y, Otsuka T, Losdat S, Häner JD, Lonborg J, et al. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. JAMA. 2022;327(18):1771-81. DOI: 10.1001/jama.2022.5218
  » https://doi.org/10.1001/jama.2022.5218
• ¹⁴
  Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. N Engl J Med. 2017;377(12):1119-31. DOI: 10.1056/NEJMoa1707914
  » https://doi.org/10.1056/NEJMoa1707914
• ¹⁵
  Bouabdallaoui N, Tardif JC, Waters DD, Pinto FJ, Maggioni AP, Diaz R, et al. Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). Eur Heart J. 2020;41(42):4092-9. DOI: 10.1056/NEJMoa1707914
  » https://doi.org/10.1056/NEJMoa1707914

Publication Dates

• Publication in this collection
  19 Dec 2022
• Date of issue
  Dec 2022