![]() ![]() According to the Food and Drug Administration (FDA), FNs should not be used by patients with high-risk conditions, such as those with Marfan syndrome or aortic diseases. Moreover, FN exposure was reported to be associated with an increased risk of adverse outcomes in AAD patients. According to different population-based studies, FN use increases the risk of AAD with a hazard ratio from 1.31 to 2.43. However, many studies have indicated that FNs are associated with an increased incidence of AAD. FNs, which are broad-spectrum antibiotics, have good tissue and cell penetration abilities. However, the specific molecular mechanism of aortic wall degeneration has yet to be fully elucidated.įluoroquinolones (FNs) are among the most commonly used antibiotics in clinical practice and have been used to treat various infectious diseases, including infectious aortic aneurysms. Increasing amounts of evidence show that the loss and dysfunction of VSMCs can induce AAD formation. However, when VSMCs are injured and stimulated, they secrete proinflammatory cytokines and matrix metalloproteinases (MMPs) that degrade the ECM of blood vessels and recruit inflammatory cells to aggravate the inflammatory response, thus destroying the aortic structure and function. Under physiological conditions, VSMCs can synthesize ECM components. The aortic media is composed mainly of VSMCs and ECM, which jointly maintain the contractile function and structural stability of the aorta. VSMCs are the most important cellular components of the aortic media and play a central role in establishing and maintaining aortic homeostasis. ![]() The critical histopathologic feature of AAD is medial degeneration characterized by vascular smooth muscle cell (VSMC) changes, extracellular matrix (ECM) degradation, and inflammation. Our results will provide novel insights into the pathogenic mechanism of fluoroquinolones in aortic diseases.Īortic dissection and aneurysm (AAD) is a cardiovascular emergency involving the separation and/or dilation of the aortic wall, and with fatal consequences if therapy is not performed in time. Functional analysis of the PPI module showed that the MAPK signalling pathway, focal adhesion, apoptosis, regulation of actin cytoskeleton, and PI3K-Akt signalling pathway were significantly enriched. Protein–protein interaction (PPI) analysis and module construction of the 34 potential CIP targets and 37 selected hub molecules after CIP stimulation identified four critical target proteins in the module: PARP1, RAC1, IGF1R and MKI67. CIP targets were predicted with online databases and verified by molecular docking. The functional analysis emphasized the important roles of metabolism, extracellular matrix homeostasis, mitochondrial damage, focal adhesion, and apoptosis in CIP-stimulated VSMCs. A total of 1351 differentially expressed proteins were identified in human aortic vascular smooth muscle cells (VSMCs) after ciprofloxacin (CIP) stimulation. This study aimed to investigate the potential functional mechanism and molecular targets of fluoroquinolones in relation to AAD by an integrated proteomic and network pharmacology strategy. Recently, fluoroquinolones have been reported to significantly increase the risk of AAD. Aortic aneurysm and dissection (AAD) is a life-threatening disease worldwide. ![]()
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