Chronic heated tobacco product serum induced cardiac fibroblast apoptosis 1.5-fold and polarized monocytes to M1 macrophages (88.9%) similar to traditional cigarettes.
Does exposure to serum from chronic heated tobacco product smokers induce inflammatory crosstalk and macrophage activation in cardiac fibroblasts and endothelial cells compared to non-smokers?
Chronic heated tobacco product smoking induces a pro-inflammatory circulating cytokine profile that promotes macrophage activation and inflammatory crosstalk in cardiac stromal and endothelial cells, similar to traditional cigarettes.
Tasa de eventos absoluta: 0% vs 0%
Abstract Introduction Tobacco combustion cigarettes (TCCs) are a risk factor for cardiovascular diseases. Heated tobacco products (HTPs) gained popularity as TCC alternatives, yet their long-term health effects remain poorly understood. Chronic HTP smokers exhibit endothelial dysfunction, oxidative stress markers, and microRNA profiles comparable to those of TCC smokers (1,2), and HTP serum activates human cardiac fibroblasts allowing their transition to matrix producing fibroblasts (3). The mechanism for fibrotic response in cardiac stromal cells has not been described. However, macrophages interact with this cell population, mediate its paracrine response and enhance fibrosis. This study investigates the inflammatory crosstalk between human endothelial cells, cardiac fibroblasts (hCFs) and macrophages in response to serum from chronic HTP smokers. Methods Primary hCFs were derived from atrial tissue obtained during elective cardiac surgeries, human monocytes were isolated from healthy volunteers.Serum was isolated from smokers and age matched non-smokers (NS). All protocols adhered to the Declaration of Helsinki. To model endothelium, human umbilical vein endothelial cells (HUVECs) were used. Results Flow cytometry analysis of apoptosis in hCFs exposed to sera from each experimental group, by annexin V/7AAD staining, revealed a 1.5-fold increase in early apoptotic cells following TCC and HTP serum treatment compared to NS serum (N=3, p0.01). However, only TCC treatment induced a significant rise in late apoptotic (annV+/7AAD+) cells (p0.05). GO analysis of the cytokines secreted by hCFs upon HTP serum exposure (FDR0.0001) highlighted leukocyte and neutrophil chemotaxis, cytokine signaling, and inflammatory response pathways. Hence the stromal-immune interactions were investigated revealing that conditioned medium from HTP serum-treated hCFs polarized CD14+ monocytes into M1 macrophages at levels comparable to TCC treatment, as assessed by CD86+/CD163- expression (N=3, 88.9% HTP vs. 93.8% TCC vs. 0.7% NS). The effect of smoke on endothelial cells was assessed, as this cell type is central in mediating macrophages activation. We focused on microRNAs expressed in HUVECs, and with the capacity to polarize macrophages, and quantified miRNAs associated with macrophages polarization in HUVECs exposed to cigarette smoke in vitro. We found increased miR-155 (FC=1,5 vs CTR, p0,05), miR-29a (FC=2,5 vs CTR p0,001) and miR29c (FC=11 vs CTR p0,001) in the cells, and found that these miRNAs are actively secreted by HUVECs. We quantified the expression of these miRNAs in the sera of healthy subjects exposed to both TCC and HNBC. Conclusions Chronic HTP smoking is associated with an inflammatory circulating cytokine profile, which can affect cardiac fibroblasts, and foster a pro-inflammatory stromal-immune cells crosstalk, inducing macrophage activation. Endothelial cells exposed to smoke can release microRNAs involved in macrophages polarization.
Pagano et al. (Sat,) reported a other. Chronic heated tobacco product serum induced cardiac fibroblast apoptosis 1.5-fold and polarized monocytes to M1 macrophages (88.9%) similar to traditional cigarettes.