GLUT1 Mediates the Metabolic Reprogramming and Inflammation of CCR2$^+$ Monocytes/Macrophages from Patients with DCM

Background: Macrophages expressing CC chemokine receptor 2 (CCR2) possess characteristics and performance akin to M1 polarized macrophages, which promote inflammation. Advanced heart failure (HF) patients with higher abundance of CCR2+ macrophages are more likely experience adverse remodeling. The precise mechanism in how they affect the progression dilated cardiomyopathy remains unknown. Methods: Cardiac biopsy samples from (DCM) were used for immunohistochemistry immunofluorescence staining. PCR is employed identify IL-1β, IL-6, TNF-α, TGF-β, MMP2, MMP9, PKM1, GLUT1, GLUT2, GLUT3, GLUT4, PDK1, PFKFB3, PFK1 HK2 mRNA expression monocytes/macrophages peripheral blood DCM patients. Seahorse was evaluate oxygen consumption rate (OCR) extracellular acidification (ECAR) monocytes/macrophages. 2-DG simulate a lack glucose. Lentivirus containing GLUT1 inhibitory sequence knockdown gene Western Blot staining NLRP3. Results: Immunostaining results cardiac tissue demonstrated that HF associated an increase number macrophages. CCR2 monocytes derived expressed elevated levels inflammatory factors up regulation glycolysis related genes. In addition, OCR glucose uptake experiments confirmed increased these cells greater inflammation correlated worsening function. limiting supply or suppressing activity transporter 1 (GLUT1) could reduce levels. Conclusions: These suggest rely on metabolic reprogramming trigger response contribute myocardial injury DCM.