Aging-Related Accumulation of Truncated Oxidized Phospholipids Augments Infectious Lung Injury and Endothelial Dysfunction via Cluster of Differentiation 36-Dependent Mechanism

• Published in: Cells (Basel, Switzerland) Vol. 12; no. 15; p. 1937
• Main Authors: Ke, Yunbo, Karki, Pratap, Li, Yue, Promnares, Kamoltip, Zhang, Chen-Ou, Eggerman, Thomas L, Bocharov, Alexander V, Birukova, Anna A, Birukov, Konstantin G
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.07.2023; MDPI
• Subjects: Aging; Atherosclerosis; Bacterial infections; bacterial pathogens; Blood circulation; Bronchus; CD36; CD36 antigen; Cell activation; Cell culture; Cell permeability; Development and progression; Endothelial cells; Endothelium; Experiments; Gene expression; Glycoproteins; Health aspects; Infections; Inflammation; Laboratories; Lavage; Lung diseases; lung injury; Lungs; Older people; Oxidation; Oxidative stress; oxidized phospholipids; Penicillin; Permeability; Phospholipids; United States; United States > US; short amphipathic helical peptides; lung injury; inflammation; L37pA; oxidized phospholipids; CD36; aging; bacterial pathogens
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12151937

Truncated phospholipid oxidation products (Tr-OxPL) increase in blood circulation with aging; however, their role in the severity of vascular dysfunction and bacterial lung injury in aging groups remains poorly understood. We investigated the effects of six Tr-OxPL species: KOdiA-PC, POVPC, PONPC, PGPC, Paz-PC, and Lyso-PC on endothelial dysfunction and lung inflammation caused by heat-killed (HKSA) in young (aged 2-4 months) and old (aged 12-18 months) mice, organotypic culture of precisely cut lung slices, and endothelial cells (mLEC) isolated from young and old mice. HKSA and Tr-OxPL combination caused a higher degree of vascular leak, the accumulation of inflammatory cells and protein in bronchoalveolar lavage, and inflammatory gene expression in old mice lungs. HKSA caused a greater magnitude of inflammatory gene activation in cell and ex vivo cultures from old mice, which was further augmented by Tr-OxPLs. L37pA peptide targeting CD36 receptor attenuated Tr-OxPL-induced endothelial cell permeability in young and old mLEC and ameliorated KOdiA-PC-induced vascular leak and lung inflammation in vivo. Finally, CD36 knockout mice showed better resistance to KOdiA-PC-induced lung injury in both age groups. These results demonstrate the aging-dependent vulnerability of pulmonary vasculature to elevated Tr-OxPL, which exacerbates bacterial lung injury. CD36 inhibition is a promising therapeutic approach for improving pneumonia outcomes in aging population.