Angiology: Open Access
Open Access

Post-Angioplasty Changes in Circulating Pro-Inflammatory Cytokines and their Clinical Implications

Steven Salberg^{* *}Correspondence: Steven Salberg, Department of Cardiovascular Medicine, University of Hamburg, Hamburg, Germany, Email:

Author info »

Description

Percutaneous Coronary Intervention (PCI), commonly known as angioplasty, is a foundation of treatment for patients with Coronary Artery Disease (CAD), particularly for those with significant atherosclerotic blockages. PCI involves the use of a balloon catheter to dilate narrowed coronary arteries and restore blood flow to the heart, often followed by stent implantation to maintain vessel patency [1].

Pro-inflammatory cytokines: Roles and mechanisms

Pro-inflammatory cytokines, including Tumor Necrosis Factoralpha (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and CReactive Protein (CRP), are central to the body’s response to injury and infection. In the context of PCI, these cytokines play a significant role in mediating the inflammatory reaction that follows arterial injury [2].

TNF-α: As one of the key pro-inflammatory cytokines, TNF-α is involved in the initiation of the inflammatory cascade. It is produced primarily by macrophages, endothelial cells, and smooth muscle cells in response to endothelial injury. Following PCI, TNF-α contributes to the activation of inflammatory pathways, including the expression of adhesion molecules on endothelial cells, which facilitates the recruitment of leukocytes to the site of injury [3].

IL-6: This cytokine is produced by a variety of cell types, including macrophages, endothelial cells, and smooth muscle cells. IL-6 plays a pivotal role in the systemic inflammatory response and is a major regulator of the acute-phase response. Elevated IL-6 levels after PCI are associated with endothelial dysfunction, increased oxidative stress, and the promotion of atherosclerotic plaque instability. IL-6 has also been linked to the development of restenosis by enhancing smooth muscle cell migration and proliferation in the vascular wall [4].

IL-1β: Another important pro-inflammatory cytokine, IL-1β is produced by macrophages and plays a critical role in the induction of fever, the activation of the immune system, and the promotion of tissue repair. Post-PCI, IL-1β contributes to the inflammatory process by stimulating the expression of adhesion molecules on endothelial cells and enhancing the activation of matrix metalloproteinases, enzymes that degrade the extracellular matrix and promote plaque rupture [5,6].

C-Reactive Protein (CRP): Although CRP is not a cytokine, it is a key acute-phase reactant that is strongly influenced by cytokine activity, particularly IL-6. CRP is widely recognized as a marker of systemic inflammation and has been extensively studied as a predictor of cardiovascular risk. Elevated CRP levels after PCI are associated with an increased risk of recurrent cardiovascular events, including myocardial infarction and stroke.

Dynamics of cytokine changes post-PCI

Early post-PCI inflammatory response: Immediately following PCI, there is a rapid increase in the levels of TNF-α, IL-6, IL-1β, and CRP. This acute-phase response is largely attributed to the mechanical injury caused by the procedure itself, including endothelial exposure and the stretching of the arterial wall. These changes promote the activation of inflammatory cells and the release of cytokines, which facilitate the healing process by recruiting immune cells to the site of injury [7].

Peak cytokine levels: Studies have shown that cytokine levels, particularly IL-6 and TNF-α, peak within the first 24 to 48 hours post-PCI. The early inflammatory response is essential for initiating tissue repair, but excessive or prolonged elevation of these cytokines can lead to undesirable effects, such as increased thrombotic risk and the promotion of restenosis. Elevated TNF- α, for example, has been associated with an increased risk of stent thrombosis, a potentially life-threatening complication following PCI.

Resolution of inflammation: After the initial peak, cytokine levels typically decline as the acute inflammatory response resolves. However, the resolution phase is not always complete, especially in patients with pre-existing inflammation or those at high cardiovascular risk. In some cases, persistent elevation of pro-inflammatory cytokines, particularly IL-6 and CRP, can contribute to chronic inflammation, endothelial dysfunction, and ongoing atherosclerotic progression, which may increase the risk of future cardiovascular events [8].

Clinical Implications of Post-PCI Cytokine Changes

Restenosis and stent thrombosis: One of the primary concerns following PCI is restenosis, the re-narrowing of the coronary artery due to neointimal hyperplasia. Pro-inflammatory cytokines, particularly TNF-α and IL-6, play a key role in this process by promoting smooth muscle cell proliferation and migration. Persistent elevation of these cytokines can contribute to the development of restenosis, which occurs in a significant proportion of patients, particularly those who are not treated with Drug-Eluting Stents (DES) or who have high-risk features.

Long-term cardiovascular risk: Chronic inflammation, as evidenced by persistently elevated cytokine levels, is a wellestablished risk factor for the progression of atherosclerosis and the development of future cardiovascular events. Elevated CRP levels, in particular, have been shown to be a predictor of recurrent myocardial infarction, stroke, and mortality. As such, monitoring cytokine levels after PCI, especially in high-risk patients, could provide valuable information for identifying those at increased risk of adverse long-term outcomes [9].

Therapeutic implications: Given the role of inflammation in post-PCI complications, targeting the inflammatory response may provide therapeutic benefits. Statins, for example, have been shown to reduce the levels of inflammatory markers such as CRP and IL-6, thereby decreasing the risk of restenosis and adverse cardiovascular events. Other potential anti-inflammatory therapies, such as IL-1β inhibitors or TNF-α blockers, are under investigation for their potential to reduce inflammation and improve outcomes in patients undergoing PCI.

Personalized care and monitoring: With a better understanding of the role of cytokines in post-PCI outcomes, clinicians may consider personalized strategies for monitoring and treating patients. Regular measurement of inflammatory markers, particularly CRP and IL-6, could help identify patients who are at higher risk for complications such as restenosis and stent thrombosis. This could allow for more modified interventions, including intensified anti-inflammatory therapy or closer followup to manage long-term risk [10].

Conclusion

Post-angioplasty changes in circulating pro-inflammatory cytokines play a central role in the body’s response to PCI and have significant clinical implications for both short- and longterm patient outcomes. While the inflammatory response following PCI is an essential part of the healing process, persistent or excessive inflammation can contribute to restenosis, thrombosis, and increased cardiovascular risk. Monitoring cytokine levels and developing targeted anti-inflammatory therapies may provide valuable strategies for improving the prognosis of patients undergoing PCI, particularly those at high risk for adverse outcomes.

References

1. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):1135-1143.

   [Crossref] [Google Scholar] [PubMed]

2. Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12(3):204-212.

   [Crossref] [Google Scholar] [PubMed]

3. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Anti-inflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119-1131.

   [Crossref] [Google Scholar] [PubMed

4. Liuzzo G, Buffon A, Biasucci LM, Gallimore JR, Caligiuri G, Vitelli A, et al. Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina. Circulation. 1998;98(22):2370-2376.

   [Crossref] [Google Scholar] [PubMed]

5. Solheim S, Grøgaard HK, Hoffmann P, Arnesen H, Seljeflot I. Inflammatory responses after percutaneous coronary intervention in patients with acute myocardial infarction or stable angina pectoris. Scand J Clin Lab Invest. 2008;68(7):555-562.

   [Crossref] [Google Scholar] [PubMed]

6. Qi X, Peng Y, Gu J, Li S, Zheng S, Zhang J, et al. Inflammatory cytokine release in patients with unstable angina after coronary angioplasty. Jpn Heart J. 2002;43(2):103-115.

   [Crossref] [Google Scholar] [PubMed]

7. Tanajura da Silva T, Junior RA, de Moura DL, Santos JC, Müller da Fonseca. Effects of coronary angioplasty on inflammatory markers and lipid profile in patients with cardiovascular disease. Biomark Med.. 2020;10(1).

   [Crossref] [Google Scholar] [PubMed]

8. Hakki S, Robinson EJ, Robson MG. Circulating Interleukin-6 and CD16 positive monocytes increase following angioplasty of an arteriovenous fistula. Sci Rep. 2022;12(1):1427.

   [Crossref] [Google Scholar] [PubMed]

9. Post MJ, de Smet BJ, van der Helm Y, Borst C, Kuntz RE. Arterial remodeling after balloon angioplasty or stenting in an atherosclerotic experimental model. Circulation. 1997;96(3):996-1003.

   [Crossref] [Google Scholar] [PubMed]

10. Virmani R, Farb A, Burke AP. Coronary angioplasty from the perspective of atherosclerotic plaque: Morphologic predictors of immediate success and restenosis. Am Heart J. 1994;127(1):163-179.

    [Crossref] [Google Scholar] [PubMed]