The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease

Homocysteine Activates B Cells via Regulating PKM2-Dependent Metabolic Reprogramming

“…A recent investigation focusing on hematopoietic stem and multipotential progenitor cells has shown that glucose transporter 1 deficiency prevents hematopoietic stem and multipotential progenitor cell proliferation, myelopoiesis and the recruitment of Ly6C hi monocytes in atherosclerotic lesions, and eventually reduces atherosclerosis in ApoE 2/2 mice (42). Actually, the most recent report on this topic has demonstrated an overexpression of PKM2 in ex vivo-generated macrophages collected from patients with coronary artery disease compared with expression in those from healthy controls and has shown that PKM2 is required for M1 polarization and proinflammatory cytokine secretion from these coronary artery disease macrophages (43). Our present study shows that the PKM2 inhibitor SKN ameliorates HHcy-accelerated atherosclerosis in ApoE 2/2 mice.…”

Pyruvate controls the checkpoint inhibitor PD-L1 and suppresses T cell immunity

“…Macrophages from CAD patients are metabolically reprogrammed and have a signature of excessive glucose uptake, increased glycolytic activity, and exuberant mitochondrial activity resulting in high levels of intracellular ROS. ROS overload modifies the glycolytic enzyme pyruvate kinase M2 (PKM2), favoring dimer formation, and enables PKM2 import into the nucleus, where the enzyme "moonlights" as a protein kinase, phosphorylates STAT3, and turns the cell into an IL-1β and IL-6 hyperproducer (24,25). Changes in the M2 isoform of pyruvate kinase, shared by inflammatory macrophages and cancer cells, have metabolic consequences that possibly affect the cells' functional behavior.…”

“…One consequence is the dimerization of the glycolytic enzyme PKM2, which promotes the production of IL-6 and IL-1β and renders the macrophages hyperinflammatory (24).…”

“…+ monocytes, which differentiate into proinflammatory effector macrophages (23,24). Macrophages from CAD patients are metabolically reprogrammed and have a signature of excessive glucose uptake, increased glycolytic activity, and exuberant mitochondrial activity resulting in high levels of intracellular ROS.…”

Envolvimento da enzima Piruvato Quinase M2 (PKM2) na diferenciação de linfócitos Th17 e patogênese da encefalomielite autoimune experimental

“…Além disso, estas estratégias conferiram maior proteção à camundongos submetidos à endotoxemia por LPS (lipopolissacarídeo) e modelo de sepse letal (CLP; Cecal Ligation Puncture) (YANG et al, 2014b aterosclerose. Utilizando um ativador que força a tetramerização da PKM2, impedindo sua translocação para o núcleo, reduziu consideravelmente os níveis de citocinas inflamatórias produzidos por estes macrófagos, corroborando com a ideia de que PKM2 é importante para a função efetora destas células (SHIRAI et al, 2016).…”