Plasma proteomics identified 331 proteins, including immune-related pathways, significantly associated with impaired coronary flow reserve (median CFR 3.2) in 44 ANOCA patients.
Are specific plasma proteins and immune pathways associated with impaired coronary flow reserve in patients with ANOCA?
Plasma proteomics identifies immune-related pathways, including interleukin and TGF-β signaling, as being associated with impaired coronary flow reserve in ANOCA patients.
Absolute Event Rate: 0% vs 0%
Abstract Background Angina with nonobstructive coronary arteries (ANOCA) affects nearly half of the patients tested for ischemic heart disease, with a higher prevalence in women. ANOCA encompasses diverse endotypes of coronary vasomotor dysfunction, including coronary microvascular dysfunction (CMD), which is characterized by an impaired coronary flow reserve (CFR). An impaired CFR is strongly associated with a lower quality of life and increased cardiovascular risk. However, the mechanisms underlying a low CFR remain largely unknown. Therefore, we performed plasma proteomics to identify pathways associated with a low CFR in ANOCA patients. Purpose To determine protein biomarkers and molecular pathways that are associated with a low CFR in ANOCA patients. Methods ANOCA patients that underwent coronary function testing (CFT) were invited to participate in the study for blood withdrawal. Plasma was isolated and used to interrogate 11,083 circulating proteins using the aptamer-based SomaScan assay. CFR was measured during CFT as absolute CFR using intracoronary continuous thermodilution or as bolus CFR using bolus thermodilution. Linear regression analysis was performed to identify associations between CFR and individual proteins. In addition, the set of proteins associated with CFR based on nominal p-value of 0.05 was tested for pathway enrichment using the Reactome and KEGG databases. Results The study included 44 patients (82% female) with a median age of 61 years and a median CFR of 3.2. After quality control, 10,491 plasma proteins were analyzed in all patients. A total of 331 proteins were significantly associated with CFR. Among the top significant proteins, we identified CPB2, ADAM15 and NLRP3 to be positively associated and SMIM3, BIK and CFHR1 to be negatively associated with CFR. Pathway enrichment analysis revealed immune-related pathways, including signaling by interleukins and cytokine-cytokine receptor interaction (CNTFR, IL11RA, OSMR, IL12A|IL12B, IL17F, IL17C, CD80, IRF4) and TGF-β signaling (TGFB1, TGFBR3) (Figure 1). Conclusions This preliminary plasma proteomics analysis suggests a role for the immune system in ANOCA patients with a low CFR. While the exact pathophysiological mechanisms remain unclear, the identification of these known immune-related proteins provides a starting point to investigate inflammatory contributions to impaired coronary flow regulation in ANOCA. Future studies should aim to validate these findings in larger cohorts to further elucidate the role of inflammation in ANOCA pathophysiology and identify potential therapeutic targets.
Jong et al. (Sat,) reported a other. Plasma proteomics identified 331 proteins, including immune-related pathways, significantly associated with impaired coronary flow reserve (median CFR 3.2) in 44 ANOCA patients.