Abstract
Background
Acute inflammatory responses during and after percutaneous coronary intervention (PCI) are associated with subsequent cardiovascular event risk, but limited data exist on acute immune cell responses regulating PCI-related inflammation. As an exploratory pilot study, our objective was to determine whether PCI acutely alters neutrophil-specific components of activation, maturity and chemotaxis in the coronary and peripheral circulation.
Methods
This prospective cohort study was conducted from October 2024 to January 2025 within an urban tertiary-care academic medical centre. Twenty-nine consecutive patients ≥18 years of age undergoing clinically indicated PCI were included. Paired blood samples were collected immediately pre-PCI and post-PCI from the peripheral arterial sheath (peripheral circulation) and coronary guide catheter (coronary circulation).
Results
The primary endpoints were pre-PCI to post-PCI changes in immature neutrophils (CD10−CD16− subset as a total percentage of neutrophils) and neutrophil-specific expression of markers relevant for activation and degranulation (CD62L and CD63 expression). In the immediate pre-PCI to post-PCI period, there was an acute increase in CD10-CD16- neutrophil subset in the coronary blood (1.5±0.3% vs 3.4±0.8%, p=0.012) and a decrease in CD62L neutrophil expression in both the coronary (median fluorescence intensities (MFI)=1340.4±102.3 vs 1084.0±92.8, p=0.002) and peripheral circulation (CD62L MFI=1182.4±82.7 vs 1078.1±77.9, p=0.035). No differences were observed with neutrophil degranulation, chemotaxis or migration.
Conclusions
In patients undergoing PCI, we observed an acute increase in circulating neutrophil cell-specific activation and immaturity markers following PCI but no significant effects of PCI on neutrophil degranulation. Further research is needed to understand whether these effects contribute to long-term post-PCI outcomes and, if so, if neutrophil release and activation warrant targeting during PCI.
Keywords: Percutaneous Coronary Intervention, Inflammation, NEUTROPHILS, CORONARY ARTERY DISEASE, Translational Medical Research
WHAT IS ALREADY KNOWN ON THIS TOPIC
Percutaneous coronary intervention (PCI) elicits local and systemic inflammation, reflected by an acute increase in circulating biomarkers such as high-sensitivity C reactive protein and neutrophil-to-lymphocyte ratio, which are associated with larger infarct size and adverse peri-procedural outcomes. However, limited data exist on acute immune cell responses, particularly neutrophil phenotype and activation profile, regulating PCI-related inflammation.
WHAT THIS STUDY ADDS
Using paired pre-PCI and post-PCI coronary and peripheral blood sampling, this study demonstrates that PCI acutely increases CD10-CD16- immature neutrophils in the coronary blood and induces neutrophil activation (reflected by CD62L shedding) in both the coronary and peripheral blood. No differences were observed with neutrophil degranulation, chemotaxis or migration.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Our findings of neutrophil-specific activation and immaturity markers immediately post-PCI, if linked to subsequent adverse clinical events, may warrant development of more targeted, neutrophil-directed therapeutic strategies in the peri-PCI period to improve patient outcomes.
Introduction
Percutaneous coronary intervention (PCI) elicits a local and systemic inflammatory response, inducing endothelial damage and release of intraplaque proinflammatory debris, with the potential to contribute to reperfusion injury.1,3 Post-PCI increases in high-sensitivity C reactive protein are associated with higher cardiac injury biomarker levels.1 These alterations in circulating inflammatory indices of inflammation are also reflected in acute changes in neutrophil-to-lymphocyte ratio, a proxy of systemic inflammation, which peaks at approximately 24 hours post-PCI and is linked to a larger infarct size and increased risk for adverse outcomes following myocardial infarction (MI).4
Despite emerging data on systemic inflammatory alterations during the peri-PCI period, limited insights exist into acute changes in immune cell phenotype and activation profile during the peri-PCI period. Identifying precise cellular alterations underlying PCI-related inflammation is of potential clinical relevance given equipoise from recent clinical trials broadly targeting inflammation in individuals undergoing PCI following MI.5,7 Therefore, using serial intraprocedural collection of whole blood from coronary guide catheters and peripheral sheaths before and after PCI with stenting, we investigated acute intraindividual, PCI-related changes in circulating immune cell phenotypes and activation profiles. As a pilot study, we were particularly interested in exploring neutrophil phenotype and activation profile given the role of neutrophils in acute immune response as well as in immature and progenitor cells given their release during acute stressors.8 Our primary hypothesis was that neutrophils exhibit a more activated phenotype detectable in the circulation in the acute post-PCI period, compared with the immediate pre-PCI period, and that these differences manifest in both coronary and peripheral circulation.
Methods
Study design and sampling
This study was approved by the Northwestern University Institutional Review Board (IRB #: STU00211813) and all subjects provided written informed consent before participating in the study. Patients undergoing planned or possible PCI were approached for consent at a single urban tertiary centre between October 2024 and January 2025; consenting patients who had pre-PCI and post-PCI blood drawn according to study protocol and underwent clinically indicated PCI with stenting were included in the study. All patients were fasting for at least 6 hours prior to procedure. Patients with a history of in-stent restenosis or organ transplant were excluded. Arterial blood samples were collected from the peripheral arterial sheath and from the coronary guide at two time points: (1) immediately prior to coronary wire insertion and (2) immediately prior to coronary guide removal. Additional details regarding clinical and blood sampling are included in online supplemental appendix as well as details of laboratory experimentation and analyses.
In brief, immediately after each blood sampling collection, polymorphonuclear leukocytes (PMNs), peripheral blood mononuclear cells (PBMCs) and plasma were isolated. Through flow cytometry, fresh PMNs were stained and gated via size exclusion using forward scatter (FSC) and side scatter (SSC), followed by CD45+ gating, and then CD11b+CD66b+ gating to find our neutrophil population of interest. CD11b+CD66b+ PMNs were subsequently analysed for activation (CD62L, CD63), viability (annexin V, Zombie NIR live-dead) and maturation (CD10, CD16) markers. PBMCs were isolated via FSC and SSC size exclusion, removal of dead cells (Zombie NIR live-dead) and gated for CD45dim hematopoietic stem and progenitor cell populations. T cells (CD3), B cells (CD20), natural killer cells (CD56) and myeloid lineage-positive (CD64) were removed. CD45dim cells were further analysed for immaturity markers (CD34, CD33, CD133 and CD117). Plasma samples were assessed for 29 different cytokines and chemokines by the prespecified V-PLEX Human Cytokine 29-Plex Kit following the manufacturer protocol (Meso Scale Diagnostics). All statistical analyses were performed using GraphPad Prism V.9. For our prespecified coprimary endpoints of intraindividual pre-to-post-PCI change in markers of (1) immature neutrophils (as percentage of total neutrophils), (2) neutrophil activation (measured as lower CD62L expression) and (3) neutrophil degranulation (measured as greater CD63 expression), a p<0.05 was considered statistically significant. Separate analyses were considered exploratory with a p<0.05, indicating possible significance.
Results
29 consecutive eligible patients were included (table 1). Mean age was 69.4 years, all were taking statin therapy, and most (22/29=76%) did not have concomitant heart failure. The majority of interventions involved the left anterior descending artery, and the average length of time from sheath placement to removal was 62 min, ranging from 14 min to 200 min.
Table 1. Patient demographic and baseline characteristics.
| Parameter | Participants (n=29) |
|---|---|
| Age, mean (SD), years | 69 (59–69) |
| Race and ethnicity, number (%)* | |
| NH White | 18 (62) |
| NH African American/Black | 5 (17) |
| NH Asian | 2 (7) |
| Hispanic | 2 (7) |
| Did not disclose | 2 (7) |
| Male, number (%) | 22 (76) |
| BMI, mean (SD)† | 28.5 (6) |
| Smoking status, number (%) | |
| Never | 14 (48) |
| Former smoker | 15 (52) |
| Current smoker | 0 (0) |
| Comorbidities, number (%)‡ | |
| Hypertension | 22 (76) |
| Diabetes | 11 (38) |
| ESRD | 1 (3) |
| HFpEF | 1 (3) |
| HFrEF | 6 (21) |
| No HF | 22 (76) |
| Statin use, number (%) | 29 (100) |
| LVEF %, mean (SD) (n=23) | 55.6 (16) |
| Left heart catheterisation indication, number (%) | |
| Angina | 4 (14) |
| Abnormal stress test | 4 (14) |
| History of CAD | 12 (41) |
| Chronic total occlusion | 7 (24) |
| ACS | 2 (7) |
| Unstable angina | 1 (3) |
| NSTEMI | 1 (3) |
| STEMI | 0 (0) |
| Coronary artery intervention, number (%) | |
| Left anterior descending artery | 16 (55) |
| Left circumflex artery | 3 (10) |
| Right coronary artery | 4 (14) |
| 2 stents | 4 (14) |
| 3 stents | 2 (7) |
| Laboratory values, mean (SD)§ | |
| Total cholesterol (mg/dL) | 132.8 (30.9) |
| LDL cholesterol (mg/dL) | 63.5 (26.1) |
| Creatinine (mg/dL) | 1.3 (0.9) |
| eGFR (mL/min/1.73 m2) | 64.2 (24.8) |
| Fasting glucose (mg/dL) | 108.0 (28.1) |
| WBC count (×103 /µL) | 6.5 (1.8) |
| Haemoglobin (g/dL) | 13.1 (2.6) |
| RDW (%) | 13.7 (1.4) |
| Platelet count (×103 /µL) | 209.2 (71.7) |
| Neutrophil % (n=21) | 58.9 (8.2) |
| Lymphocyte % (n=21) | 27.5 (8.4) |
| Monocyte % (n=21) | 9.1 (2.4) |
| Eosinophil % (n=21) | 3.3 (1.7) |
| Basophil % (n=21) | 0.8 (0.3) |
Race and ethnicity were collected based via participant self-report.
Calculated as weight in kilograms divided by height in m2.
Medical history was collected via medical record review.
n denotes the available number of patients with available data for each respective parameter.
ACS, acute coronary syndrome; BMI, body mass index; CAD, coronary artery disease; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LDL, low-density lipoprotein; LVEF, left ventricular ejection fraction; NH, non-Hispanic; NSTEMI, non-ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention; RDW, red cell distribution width; STEMI, ST-segment elevation myocardial infarction; WBC, white cell count.
Using PMNs extracted from each blood sample, we performed flow cytometry and stained for prespecified markers of neutrophil maturity, activation and degranulation (figure 1). Our endpoints were pre-to-post-PCI change in markers of (1) immature neutrophils (as percentage of total neutrophils), (2) neutrophil activation (measured as lower CD62L expression) and (3) neutrophil degranulation (higher CD63 expression). Neutrophil activation, reflected as a decrease in CD62L median fluorescence intensity, was significant in both the coronary guide (1340.4±102.3 vs 1084.0±92.8, p=0.002) and peripheral sheath (1182.4±82.7 vs 1078.1±77.9, p=0.04) from pre-PCI to post-PCI. There was a significant increase in the proportion of immature neutrophils (CD10-CD16- within the overall CD11b+CD66b+ subset) from pre-to-post-PCI in the coronary guide (1.5%±0.3% vs 3.4%±0.8%, p=0.01) but not peripheral sheath (2.2%±0.5% vs 2.1%±0.4%, p=0.73). These findings were not associated with procedural duration, as time from pre-PCI to post-PCI sampling was not significantly associated with changes in CD62L expression or immature neutrophil proportion in either coronary or peripheral samples (online supplemental figure 7; online supplemental table 1). For neutrophil degranulation, there were no significant differences in neutrophil expression of CD63 from pre-to-post-PCI in the coronary guide or peripheral sheath. We explored markers of neutrophil apoptosis (online supplemental figure 1) and observed no consistent or significant difference from pre-PCI to post-PCI.
Figure 1. Changes in neutrophil maturity, activation, and degranulation following percutaneous coronary intervention (PCI). (a) Polymorphonuclear leukocytes (PMNs) were broadly selected based on their light scattering properties of the forward scatter area (FSC-A)/side scatter area (SSC-A) plot. Then, doublets and cellular aggregates were excluded by gating on FSC-A/forward scatter height (FSC-H), selecting events with proportional area and height. CD45+ cells were next gated from the CD45/SSC A plot. Finally, neutrophils that were CD66b+CD11b+ were gated based on the CD66b/CD11b plot. Within CD66b+CD11b+ subsets, subsequent analyses were performed (b)–(d). For the bar graphs representing each population of interest, data are presented as mean±SEM The asterisks (*) or (**) at the top of bars indicate significant differences of p<0.05 or p<0.01, respectively. (b) Immature PMNs were gated by CD10−CD16− population. (c) PMN activation was gated by CD63+CD62L− population and measured by CD62L median fluorescence intensity (MFI) expression. (d) PMN degranulation was measured by CD63+ MFI expression.
Given differences in neutrophil activation markers observed pre-PCI to post-PCI, we first determined whether plasma from before versus after PCI independently altered neutrophil chemotaxis. Using a single pool of healthy donor neutrophils, we performed a transmigration assay in which paired pre-PCI and post-PCI plasma from the same individuals served as the chemoattractant. We observed no significant difference in neutrophil migration for pre-PCI versus post-PCI plasma (online supplemental figure 2). Next, to explore other acute cell-extrinsic differences in plasma from pre-PCI to post-PCI, we analysed expression of 29 prespecified markers in the plasma using a commercial array (online supplemental figure 3). In the peripheral sheath, there was a significant increase from pre-PCI to post-PCI in plasma levels (pg/mL) of interferon (IFN)-γ (2.84±0.45 vs 4.25±0.71, p<0.001), IL-6 (0.86±0.14 vs 1.28±0.22, p<1×10−4), IL-10 (0.66±0.11 vs 1.19±0.33, p<1×10−4), and IFN-inducible protein (IP)−10, also known as CXCL-10 (471.4±51.1 vs 913.4±156.4, p<1×10−4). There was also a significant decrease in the plasma vascular endothelial growth factor level in the sheath (0.54±0.16 vs 0.17±0.04, p<0.001). From the coronary arterial blood taken from the guidewire, the plasma level of monocyte chemoattractant protein (MCP)-4 significantly decreased (108.3±13.7 vs 59.3±5.6, p<0.001). MCP-4 was the only cytokine that was significantly different pre-to-post-PCI in the guide plasma after Benjamini-Hochberg correction. There were no differences in the sheath plasma levels of TNF-α, IL-8, MCP-1 and IL-1β. Online supplemental figure 3 depicts the remaining cytokines that were studied in the pre-PCI and post-PCI plasma of the guide and sheath blood.
Discussion
Given PCI-associated changes in inflammatory mediators in the plasma or in broad complete blood count (CBC) subfractions that have been previously described, we aimed to define the acute peri-PCI changes in circulating neutrophils in coronary and peripheral circulation and observed an increase in circulating immature neutrophils and neutrophil activation markers. Specifically, the CD10−CD16− immature neutrophil subset was elevated in the coronary circulation following PCI, while the CD62L expression, with lower expression marking increase in neutrophil activation, was decreased in both the coronary and peripheral circulation. Meanwhile, CD63 expression, a marker of neutrophil degranulation, was no different from pre-to-post-PCI, nor were neutrophil chemotaxis markers and functional assays.
Mechanistically, several processes may underlie these acute neutrophil phenotypic changes. During PCI, the resulting mechanical plaque disruption, endothelial damage and ischaemia-reperfusion injury trigger the complement cascade and local release of alarmins and chemotactic factors, such as cytokines, myeloperoxidase and neutrophil-derived microparticles, driving further neutrophil recruitment to the area.9 10 Following an acute MI, there is a higher frequency of CD10- neutrophils in circulation in response to local myocardial injury via increased systemic concentrations of PMN chemoattractants. It is also possible that the sympathetic surge from the transient acute tissue injury and inflammation during a PCI induces emergency granulopoiesis and rapid release of immature PMNs by the bone marrow into the bloodstream, where these immature neutrophils preferentially traffic towards the coronary vasculature injury site.11 12 However, given the short procedural timeframe in our study (mean of 62 min) with de novo granulopoiesis from the bone marrow typically requiring hours to days, it is more likely that the immature PMNs rapidly mobilised from pre-existing pools, consistent with lack of association between procedural duration and changes in immature neutrophils or neutrophil activation. These may include marginated neutrophil reservoirs within local vasculature beds, such as the pulmonary circulation, or readily releasable neutrophil stores in the bone marrow, rather than de novo production. Moreover, mobilisation from these pools may have also been influenced by non-specific factors, including procedural stress, sympathetic activation or heparin administration.
The direct exposure of PMNs to the local proinflammatory coronary milieu also results in the subsequent shedding of CD62L, an early marker of PMN activation and endothelial engagement, facilitating firm adhesion and transmigration into the coronary and peripheral vasculature.13 The CD62L loss is interesting given the concomitant finding of increased immature neutrophils, which generally have high CD62L. However, immature neutrophils represented a low overall proportion of neutrophils (<5%) and were not consistently decreased in both coronary and peripheral blood; a potential explanation for this is that loss of CD62L by mature neutrophils (>95% of neutrophils) dominated overall CD62L expression.
While we observed acute PMN activation and immature neutrophil mobilisation in the immediate procedural window, evidence of full PMN degranulation, as depicted by CD63 expression, was absent. This likely reflects the fact that degranulation typically occurs in more robust inflammatory responses and later stages of neutrophil activation, whereas the peri-PCI coronary milieu may have been insufficient to trigger primary granule release. Despite these phenotypic PMN alterations, no functional changes were found in our neutrophil transmigration assay when healthy donor PMNs were exposed to pre-PCI versus post-PCI plasma from either the coronary or peripheral circulation. This may reflect a lack of change in systemic plasma chemotactic activity, although the use of healthy PMNs on diseased plasma limits our interpretation.
We also investigated whether specific alterations in the circulating plasma environment occurring acutely from pre-to-post-PCI could account for the observed phenotypic neutrophil changes. Despite previous studies reporting increases in general plasma inflammatory markers, such as plasma CRP and IL-6 following PCI, we did not observe significant alterations pre-to-post-PCI in our plasma cytokine panel, with the exception of IFN-γ, IL-6, IL-10 and IP-10 in peripheral circulation.14 It is uncertain whether this discrepancy was the result of our modest sample size relative to studies focused exclusively on plasma biomarkers or unique features of our patient cohort. Importantly, despite these limited systemic changes, we observed neutrophil activation and mobilisation at the cellular level, favouring cell-intrinsic changes as a more sensitive marker of acute peri-PCI inflammation.
Given these observations, it is important to address the potential clinical implications of our findings. Prior studies demonstrating increases in proinflammatory cytokines, combined with our observed PMN activation and mobilisation of immature PMNs in the acute peri-PCI period, raise the possibility that anti-inflammatory therapies could mitigate these responses and potentially improve post-PCI outcomes. Colchicine is of particular interest, given its direct inhibitory effects on neutrophil migration and chemotaxis. Large, randomised trials, including COLCOT and LoDoCo2, have shown that low-dose colchicine significantly reduces cardiovascular events when initiated 14 days post-MI in the setting of acute coronary syndrome (ACS) and in patients with chronic coronary syndrome (CCS), respectively.7 15 Notably, our study cohort consisted predominantly of CCS patients (n=27/29, 93%), making it more closely resemble that of the LoDoCo2 population, which demonstrated a 31% reduction in cardiovascular events in stable coronary disease.15 In contrast, CLEAR SYNERGY (OASIS-9) found that initiating low-dose colchicine during hospitalisation for acute MI (95% STEMI, 5% NSTEMI) did not reduce major adverse cardiovascular events (cardiovascular death, recurrent MI, stroke or urgent ischaemia-driven revascularisation) over 3 years, highlighting that both the timing of initiation and underlying clinical context may influence therapeutic efficacy.6 Whether targeting the PMN activation and immature neutrophil mobilisation observed in our predominantly elective PCI cohort translates into improved clinical outcomes remains uncertain and warrants further study. Ongoing trials, such as COL BE PCI, which include both ACS and CCS patients undergoing PCI, may provide additional insights into this question.16
Limitations
As a hypothesis-generating pilot study, our work has notable limitations. Procedural times of PCIs varied, which led to differences in timing from pre-to-post-PCI blood collection. To address this, we used a consistent approach to intraprocedure arterial blood draw timing prior to and immediately after coronary intervention. Nevertheless, variability between individuals in PCI timing could affect results. In addition, women comprised only 24% of our study population, limiting our ability to potentially identify sex-based differences in acute inflammatory responses, and we were not powered to perform subanalyses by other clinical covariates. Additionally, our modest sample size and limited peri-procedural observation period further restrict generalisability and preclude assessment of long-term clinical outcomes. Similarly, the lack of change in CD63 expression (degranulation) in the peri-PCI period may be attributed to a temporal limitation of our immediate post-PCI sampling, as primary azurophilic granule release requires more sustained stimulation than early activation markers, such as CD62L. Future studies with extended sampling points beyond the immediate postprocedural timeframe would help determine whether the lack of response was due to insufficient stimulation by the inflammatory milieu or if neutrophil degranulation occurs in a more delayed fashion. The absence of a control group undergoing diagnostic coronary angiography without PCI also reduces our ability to delineate neutrophil changes specific to plaque disruption and stent implantation versus those due to procedural factors such as catheter manipulation, contrast exposure or procedural stress.
Importantly, because our study was conducted in human patients undergoing clinically indicated PCI, heparin was uniformly administered, so we were not able to disentangle its pharmacological effects from procedural effects on our neutrophils. This is a notable limitation given the potential that intraprocedural anticoagulation or antiplatelet agents may have also contributed to the mobilisation of immature PMNs.17 18 Although our study was not powered to exclude pharmacological contributions, our observation, a significant increase of immature PMNs in the coronary circulation without parallel changes in the peripheral circulation, is a hypothesis-generating finding supporting the possibility of local injury as a primary driver of PMN trafficking to the site of plaque disruption more so than a systemic pharmacological effect.
Regarding other limitations, our transmigration assay was performed utilising a single pool of healthy donor neutrophils, which does not capture patient-specific neutrophil activation states that may be influenced by underlying coronary artery disease. However, this approach was intentional to isolate the chemoattractant properties of the peri-PCI plasma milieu, independent of intrinsic neutrophil ‘priming’ or activation states. Additionally, neutrophils are also highly sensitive to freeze-thaw cycles, with significant changes on viability and function. As such, our functional study does not fully account for the combined effects of the peri-PCI plasma microenvironment and intrinsic cellular activation state. Finally, although absolute neutrophil counts are clinically relevant, our analysis focused on proportional changes in neutrophil subsets. Preprocedural clinical laboratory values were available, but intraprocedural and postprocedural CBC measurements were not routinely obtained in our predominantly elective PCI cohort. However, our primary objective was to utilise flow cytometry to characterise neutrophil phenotypic subsets and activation markers, which are not captured by standard CBC parameters. Accordingly, analyses were standardised to a fixed input of 1×106 PMNs per sample, enabling consistent assessment of relative subset composition. Future studies correlating these phenotypic findings with absolute counts from paired CBC measurements and long-term clinical outcomes would enhance clinical applicability.
Conclusion
We observed an acute increase in circulating neutrophil cell-specific activation and immaturity markers following PCI, but no significant effects of PCI on neutrophil degranulation. Further research is needed to understand whether these effects contribute to long-term post-PCI outcomes and, if so, if neutrophil release and activation warrant targeting during PCI.
Supplementary material
Footnotes
Funding: This study was funded by American Heart Association (AHA) Grant: 24SFRNCCN1276086, National Institute of Health (NIH) Grant: R01HL175893.
Provenance and peer review: Not commissioned; externally peer-reviewed.
Patient consent for publication: Not applicable.
Ethics approval: This study involves human participants and was approved by Northwestern University Institutional Review Board (IRB #: STU00211813). Participants gave informed consent to participate in the study before taking part.
Data availability free text: The data underlying this study consist of deidentified participant clinical and laboratory data collected at Northwestern University. These data are not publicly available due to patient privacy and institutional restrictions. Data may be obtained from Northwestern University subject to appropriate institutional approvals and data use agreements. Requests for access may be directed to the corresponding author.
Data availability statement
Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available.
References
- 1.Tucker B, Vaidya K, Cochran BJ, et al. Inflammation during Percutaneous Coronary Intervention-Prognostic Value, Mechanisms and Therapeutic Targets. Cells. 2021;10:1391. doi: 10.3390/cells10061391. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Ramadan MM, Kodama M, Mitsuma W, et al. Impact of percutaneous coronary intervention on the levels of interleukin-6 and C-reactive protein in the coronary circulation of subjects with coronary artery disease. Am J Cardiol. 2006;98:915–7. doi: 10.1016/j.amjcard.2006.04.034. [DOI] [PubMed] [Google Scholar]
- 3.Wan M, Hu K, Lu Y, et al. Co-release of cytokines after drug-eluting stent implantation in acute myocardial infarction patients with PCI. Sci Rep. 2024;14:1236. doi: 10.1038/s41598-024-51496-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Huo LK, Chen KY, Tse G, et al. Association of inflammatory markers based on routine blood with prognosis in patients underwent percutaneous coronary intervention. Medicine (Baltimore) 2024;103:e38118. doi: 10.1097/MD.0000000000038118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Broch K, Anstensrud AK, Woxholt S, et al. Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction. J Am Coll Cardiol. 2021;77:1845–55. doi: 10.1016/j.jacc.2021.02.049. [DOI] [PubMed] [Google Scholar]
- 6.Jolly SS, d’Entremont M-A, Lee SF, et al. Colchicine in Acute Myocardial Infarction. N Engl J Med. 2025;392:633–42. doi: 10.1056/NEJMoa2405922. [DOI] [PubMed] [Google Scholar]
- 7.Tardif J-C, Kouz S, Waters DD, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019;381:2497–505. doi: 10.1056/NEJMoa1912388. [DOI] [PubMed] [Google Scholar]
- 8.Kelly LS, Darden DB, Fenner BP, et al. The Hematopoietic Stem/Progenitor Cell Response to Hemorrhage, Injury, and Sepsis: A Review of Pathophysiology. Shock. 2021;56:30–41. doi: 10.1097/SHK.0000000000001699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Serrano CV, Jr, Ramires JAF, Venturinelli M, et al. Coronary Angioplasty Results in Leukocyte and Platelet Activation With Adhesion Molecule Expression. J Am Coll Cardiol. 1997;29:1276–83. doi: 10.1016/S0735-1097(97)00070-3. [DOI] [PubMed] [Google Scholar]
- 10.Martínez GJ, Barraclough JY, Nakhla S, et al. Neutrophil-derived microparticles are released into the coronary circulation following percutaneous coronary intervention in acute coronary syndrome patients. Biosci Rep. 2017;37:BSR20160430. doi: 10.1042/BSR20160430. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Fraccarollo D, Neuser J, Moller J, et al. Expansion of CD10(neg) neutrophils and CD14(+)HLA-DR(neg/low) monocytes driving proinflammatory responses in patients with acute myocardial infarction. Elife. 2021 doi: 10.7554/eLife.66808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Keresztes M, Horváth T, Ocsovszki I, et al. ACTH- and cortisol-associated neutrophil modulation in coronary artery disease patients undergoing stent implantation. PLoS One. 2013;8:e71902. doi: 10.1371/journal.pone.0071902. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Inoue T, Sohma R, Miyazaki T, et al. Comparison of activation process of platelets and neutrophils after coronary stent implantation versus balloon angioplasty for stable angina pectoris. Am J Cardiol. 2000;86:1057–62. doi: 10.1016/s0002-9149(00)01159-0. [DOI] [PubMed] [Google Scholar]
- 14.Wu M, Gu X, Li X, et al. C-Reactive Protein and Inflammatory Cytokines during Percutaneous Coronary Intervention. J Vasc Res. 2016;53:39–48. doi: 10.1159/000447558. [DOI] [PubMed] [Google Scholar]
- 15.Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020;383:1838–47. doi: 10.1056/NEJMoa2021372. [DOI] [PubMed] [Google Scholar]
- 16.De Cock E, Kautbally S, Timmermans F, et al. Low-dose colchicine for the prevention of cardiovascular events after percutaneous coronary intervention: Rationale and design of the COL BE PCI trial. Am Heart J. 2024;278:61–71. doi: 10.1016/j.ahj.2024.08.022. [DOI] [PubMed] [Google Scholar]
- 17.Zhang S, Condac E, Qiu H, et al. Heparin-induced leukocytosis requires 6-O-sulfation and is caused by blockade of selectin- and CXCL12 protein-mediated leukocyte trafficking in mice. J Biol Chem. 2012;287:5542–53. doi: 10.1074/jbc.M111.314716. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Evangelista V, Manarini S, Dell’Elba G, et al. Clopidogrel inhibits platelet-leukocyte adhesion and platelet-dependent leukocyte activation. Thromb Haemost. 2005;94:568–77. [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available.