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The Role of CXC Chemokines in Cardiovascular Diseases.

ABSTRACT: Cardiovascular disease (CVD) is a class of diseases with high disability and mortality rates. In the elderly population, the incidence of cardiovascular disease is increasing annually. Between 1990 and 2016, the age-standardised prevalence of CVD in China significantly increased by 14.7%, and the number of cardiovascular disease deaths increased from 2.51 million to 3.97 million. Much research has indicated that cardiovascular disease is closely related to inflammation, immunity, injury and repair. Chemokines, which induce directed chemotaxis of reactive cells, are divided into four subfamilies: CXC, CC, CX3C, and XC. As cytokines, CXC chemokines are similarly involved in inflammation, immunity, injury, and repair and play a role in many cardiovascular diseases, such as atherosclerosis, myocardial infarction, cardiac ischaemia-reperfusion injury, hypertension, aortic aneurysm, cardiac fibrosis, postcardiac rejection, and atrial fibrillation. Here, we explored the relationship between the chemokine CXC subset and cardiovascular disease and its mechanism of action with the goal of further understanding the onset of cardiovascular disease.

SUBMITTER: Lu X

PROVIDER: S-EPMC9163960 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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The Role of CXC Chemokines in Cardiovascular Diseases.

Lu Xiyi X Wang Zhen Z Ye Di D Feng Yongqi Y Liu Menglin M Xu Yao Y Wang Menglong M Zhang Jishou J Liu Jianfang J Zhao Mengmeng M Xu Shuwan S Ye Jing J Wan Jun J

Frontiers in pharmacology 20220520

Cardiovascular disease (CVD) is a class of diseases with high disability and mortality rates. In the elderly population, the incidence of cardiovascular disease is increasing annually. Between 1990 and 2016, the age-standardised prevalence of CVD in China significantly increased by 14.7%, and the number of cardiovascular disease deaths increased from 2.51 million to 3.97 million. Much research has indicated that cardiovascular disease is closely related to inflammation, immunity, injury and repa ...[more]

PMID: 35668739

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Project description:The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A. Colistin-resistant K. pneumoniae isolates affected by genetic mutation of the PmrA/PmrB two-component system, a chromosomally encoded regulator of lipopolysaccharide modification, and containing 4-amino-4-deoxy-l-arabinose-modified lipid A were also found to be susceptible to chemokine-mediated antimicrobial activity. However, loss of PhoP/PhoQ autoregulatory control, caused by disruption of the gene encoding the negative regulator MgrB, limited the bactericidal effects of CXCL9 and CXCL10 in a variable, strain-specific manner. Cumulatively, these findings provide mechanistic insight into chemokine-mediated antimicrobial activity, highlight disparities amongst determinants of colistin resistance, and suggest that chemokine-mediated bactericidal effects merit additional investigation as a therapeutic avenue for treating infections caused by multidrug-resistant pathogens.IMPORTANCE As bacterial pathogens become resistant to multiple antibiotics, the infections they cause become increasingly difficult to treat. Carbapenem antibiotics provide an essential clinical barrier against multidrug-resistant bacteria; however, the dissemination of bacterial enzymes capable of inactivating carbapenems threatens the utility of these important antibiotics. Compounding this concern is the global spread of bacteria invulnerable to colistin, a polymyxin antibiotic considered to be a last line of defense against carbapenem-resistant pathogens. As the effectiveness of existing antibiotics erodes, it is critical to develop innovative antimicrobial therapies. To this end, we demonstrate that the chemokines CXCL9 and CXCL10 kill the most concerning carbapenem- and colistin-resistant pathogens. Our findings provide a unique and timely foundation for therapeutic strategies capable of countering antibiotic-resistant "superbugs."

Project description:BackgroundPancreatic cancer is one of the principal causes of tumor-related death worldwide. CXC chemokines, a subfamily of functional chemotactic peptides, affect the initiation of tumor cells and clinical outcomes in several human malignant tumors. However, the specific biological functions and clinical significance of CXC chemokines in pancreatic cancer have not been clarified.MethodsBioinformatics analysis tools and databases, including ONCOMINE, GEPIA2, the Human Protein Atlas, DAVID, GeneMANIA, cBioPortal, STRING, DGidb, MethSurv, TRRUST, SurvExpress, SurvivalMeth, and TIMER, were utilized to clarify the clinical significance and biological functions of CXC chemokine in pancreatic cancer.ResultsExcept for CXCL11/12, the transcriptional levels of other CXC chemokines in PAAD tissues were significantly elevated, and the expression level of CXCL16 was the highest among these CXC chemokines. Our findings also suggested that all of the CXC chemokines were linked to tumor-immune dysfunction involving the abundance of immune cell infiltration, and the Cox proportional hazard model confirmed that dendritic and CXCL3/5/7/8/11/17 were significantly associated with the clinical outcome of PAAD patients. Furthermore, increasing expressions of CXCL5/9/10/11/17 were related to unfavorable overall survival (OS), and only CXCL17 was a prognostic factor for disease-free survival (DFS) in PAAD patients. The expression pattern and prognostic power of CXC chemokines were further validated in the independent GSE62452 dataset. For the prognostic value of single CpG of DNA methylation of CXC chemokines in patients with PAAD, we identified 3 CpGs of CXCL1, 2 CpGs of CXCL2, 2 CpGs of CXCL3, 3 CpGs of CXCL4, 10 CpGs of CXCL5, 1 CpG of CXCL6, 1 CpG of CXCL7, 3 CpGs of CXCL12, 3 CpGs of CXCL14, and 5 CpGs of CXCL17 that were significantly associated with prognosis in PAAD patients. Moreover, the prognostic value of CXC chemokine signature in PAAD was explored and tested in two independent cohort, and results indicated that the patients in the low-risk group had a better OS compared with the high-risk group. Survival analysis of the DNA methylation of CXC chemokine signature demonstrated that PAAD patients in the high-risk group had longer survival times.ConclusionsThese findings reveal the novel insights into CXC chemokine expression and their biological functions in the pancreatic cancers, which might serve as accurate prognostic biomarkers and suitable immunotherapeutic targets for patients with pancreatic cancer.

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The Role of CXC Chemokines in Cardiovascular Diseases.

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The Role of CXC Chemokines in Cardiovascular Diseases.

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