microRNA‐107 protects against inflammation and endoplasmic reticulum stress of vascular endothelial cells via KRT1‐dependent Notch signaling pathway in a mouse model of coronary atherosclerosis

Abstract

Coronary atherosclerosis is a long‐term, sustained, and evolving inflammatory disease manifested with the remodeling of the coronary arteries. The purpose of this study is to explore the potential role of microRNA‐107 (miR‐107) in vascular endothelial cells (VECs) in coronary atherosclerosis by regulating the KRT1 gene and the Notch signaling pathway. A mouse model of coronary atherosclerosis was established. The relationship between miR‐107 and KRT1 was analyzed and verified by dual‐luciferase reporter assay. The functional role of miR‐107 in coronary atherosclerosis was determined using ectopic expression and depletion. Blood lipid levels and atherosclerotic index (AI) were measured in atherosclerotic mice. Expression pattern of miR‐107, KRT1, Notch signaling pathway, inflammatory/anti‐inflammatory factors, and endoplasmic reticulum (ER) stress‐related genes was evaluated by means of reverse transcription quantitative polymerase chain reaction, western blot analysis, and enzyme‐linked immunosorbent assay. Meanwhile, cell‐cycle distribution and cell apoptosis in VECs were assessed by flow cytometry. Atherosclerotic mice exhibited higher blood lipid levels, AI, apoptotic index, and KRT1‐positive expression as well as inhibited Notch signaling pathway when compared with normal mice. The miR‐107 was revealed to bind to KRT1; miR‐107 upregulation or KRT1 silencing resulted in reductions in blood lipid levels and AI, inhibition in cell apoptosis, inflammation, and ER stress. Restored miR‐107 or downregulated KRT1 activated the Notch signaling pathway. These results supported the notion that miR‐107‐targeted KRT1 inhibition activated the Notch pathway, thereby, protecting against the coronary atherosclerosis. Findings in this study might provide a novel biomarker for the coronary atherosclerosis treatment.

Extracellular vesicles from human cardiovascular progenitors trigger a reparative immune response in infarcted hearts

“…Although the present experiments focused on the immune-inflammatory responses to EV and, as such, did not include functional assessments, it is noteworthy that in a previous study from our laboratory 6 , EV from the same CPC source as in the present study were shown to improve post infarction contractile performance in a mouse model of chronic left ventricular dysfunction. The transcriptomic study of these EV had highlighted the strong expression of 16 microRNAs broadly conserved across species, among which at least half, i.e., miR-92a 46 , miR-24 47 , miR-93-5p 48 , miR 20b-5p 49 , miR-107 50 , miR 26a-5p 51 , miR-16-5p 52 and miR-130b-3p 53 are to some extent involved in the regulation of inflammation. It is thus plausible that the effects of the EV cargo on the mitigation of immune-inflammatory responses demonstrated in the present study participate in the previously documented EV-associated preservation of post infarction heart function.…”

iTRAQ‑based proteomic analysis reveals potential regulatory networks in dust mite‑related asthma treated with subcutaneous allergen immunotherapy

“…Keratin family proteins can promote the proliferation of epithelial cells via multiple immune response pathways, and the epidermal cells are known to serve a key role in airway remodeling during asthma (23). Previous research has indicated that KrT1 was involved in the regulation of the notch signaling pathway and affected the repair of vascular endothelial cell damage (24,25). It has been identified that the specific expression of KRT1 affects complex traits (26).…”

Role of Endoplasmic Reticulum Stress in Atherosclerosis and Its Potential as a Therapeutic Target

“…MAPK signaling has been confirmed to participate in atherosclerosis by regulating the proliferation and migration of VECs, and miR-29b downregulation attenuated atherosclerosis by suppressing the MAPK signaling pathway and inflammation in the aortas of ApoE −/− mice [ 136 ]. Another example is that miR-107 activated the Notch pathway by targeting keratin 1 (KRT1) gene inhibition, consequently protecting VECs from inflammation and ER stress in a mouse model of coronary atherosclerosis [ 137 ].…”