NF-κB activation in cardiac fibroblasts results in the recruitment of inflammatory Ly6C ^hi monocytes in pressure-overloaded hearts

Abstract

Heart failure is a major public health problem, and inflammation is involved in its pathogenesis. Inflammatory Ly6C hi monocytes accumulate in mouse hearts after pressure overload and are detrimental to the heart; however, the types of cells that drive inflammatory cell recruitment remain uncertain. Here, we showed that a distinct subset of mouse cardiac fibroblasts became activated by pressure overload and recruited Ly6C hi monocytes to the heart. Single-cell sequencing analysis revealed that a subset of cardiac fibroblasts highly expressed genes transcriptionally activated by the transcription factor NF-B, as well as C-C motif chemokine ligand 2 (Ccl2) mRNA, which encodes a major factor in Ly6C hi monocyte recruitment. The deletion of the NF-B activator IKK in activated cardiac fibroblasts attenuated Ly6C hi monocyte recruitment and preserved cardiac function in mice subjected to pressure overload. Pseudotime analysis indicated two single-branch trajectories from quiescent fibroblasts into inflammatory fibroblasts and myofibroblasts. Our results provide insight into the mechanisms underlying cardiac inflammation and fibroblast-mediated inflammatory responses that could be therapeutically targeted to treat heart failure.

Empagliflozin attenuates cardiac microvascular ischemia/reperfusion through activating the AMPKα1/ULK1/FUNDC1/mitophagy pathway

“…The relative fluorescence intensity was determined using randomly selected cross-sections of CMECs. The fluorescent intensities were extracted, and individual images were normalized to the average background intensity [ 38 ]. During quantitation, RGB images were converted to 32-bit grayscale images.…”

SGLT2 inhibitor dapagliflozin reduces endothelial dysfunction and microvascular damage during cardiac ischemia/reperfusion injury through normalizing the XO-SERCA2-CaMKII-coffilin pathways

“…Temperature was strictly maintained between 36.5 ºC and 37.5 ºC, and heart rate was maintained above 400 beats per minute to void confounding effects of hypothermia and bradycardia. B-mode short axis images and M-mode scans were collected, and analyzed following completion of the data acquisition 34 .…”

Latifolin enhances both survival and cardiomyocyte differentiation of bone marrow mesenchymal stem cells on rat myocardial infarction model

“…Activation of NF-κB produces a series of in ammatory cytokines, such as IL-6, IL-1β, IL-12, TNFa. In this in ammatory cytokines, IL-6 plays a central role in body defense by stimulating various cell populations and is an essential part of the in ammatory mediator network [39,40] . In recent years, HIF-1/ NF-κB is being increasingly recognized as a critical factor in the in ammatory response.…”