Femoral atherosclerotic plaques are less inflammatory than carotid plaques histologically, but limited cell-level data exist regarding comparative immune landscapes and polarization at these sites. We investigated intraplaque leukocyte phenotypes and transcriptional polarization in 49 patients undergoing femoral ( n = 23) or carotid ( n = 26) endarterectomy using single-cell RNA-Seq (scRNA-Seq; n = 13), flow cytometry ( n = 24), and IHC ( n = 12). Comparative scRNA-Seq of CD45 ⁺ -selected leukocytes from femoral ( n = 9; 35,265 cells) and carotid ( n = 4; 30,655 cells) plaque revealed distinct transcriptional profiles. Inflammatory foam cell–like macrophages and monocytes comprised higher proportions of myeloid cells in carotid plaques, whereas noninflammatory foam cell–like macrophages and LYVE1-overexpressing macrophages comprised higher proportions of myeloid cells in femoral plaque ( P < 0.001 for all). A significant comparative excess of CCR2 ⁺ macrophages in carotid versus plaque was observed by flow cytometry in a separate validation cohort. B cells were more prevalent and exhibited a comparatively antiinflammatory profile in femoral plaque, whereas cytotoxic CD8 ⁺ T cells were more prevalent in carotid plaque. In conclusion, human femoral plaques exhibit distinct macrophage phenotypic and transcriptional profiles as well as diminished CD8 ⁺ T cell populations compared with human carotid plaques

Acute neutrophil responses following myocardial infarction (MI) play a central role in remodeling, contributing to both repair and potential maladaptive responses. Although prior studies have investigated circulating immune cell indices at a single time point during hospitalization for MI, limited data exist on acute intra-individual changes in circulating immune profiles during evolving MI. We analyzed clinical measurements, such as the count and proportion of immune cell components in a serial complete blood count, with differential tests conducted for patients hospitalized with ST-elevation MI (STEMI) in various hospitals in the Northwestern Medicine system from 1 January 2002 to 1 August 2024. Patients with STEMI diagnosis, troponin peaks ≥ 5 ng/mL, and cell count and proportion data prior to the troponin peak and within 24 h after the troponin peak were included. Primary analyses investigated the associations between the troponin peak and peri-STEMI changes in immune cell subsets. Multivariable-adjusted Cox models were used to investigate associations between these peri-STEMI immune cell changes and mortality at 1 year and 3 years. Among the 694 STEMI patients meeting the inclusion criteria, a higher troponin peak was associated with a modest peri-MI increase in neutrophil proportion. Higher adjusted peri-STEMI increases in neutrophil count and proportion were strongly associated with mortality at one and three years [hazard ratio (HR) = 1.31 (95% confidence interval (CI) 1.15–1.49) and HR = 1.27 (95% CI 1.14–1.45) per 1000 cells/μL absolute neutrophil increase, respectively]. Individuals with higher STEMI-related neutrophil increases had higher mortality at one year and three years, independent of the extent of troponin elevation.

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.