The dual role of metabolic reprogramming in macrophage polarization in rheumatoid arthritis and coronary heart disease and the intervention strategy of traditional Chinese medicine.

Macrophage polarization has become increasingly acknowledged as a process that is governed by metabolism which will have significant impacts on long-term inflammatory and cardiovascular diseases. Through the atherosclerotic component of coronary pathology, both rheumatoid arthritis and coronary heart disease result in macrophages undergoing dramatic metabolic changes that ultimately determine how they functionally behave in terms of their inflammatory characteristics. While pro-inflammatory M1 macrophages exhibit a preference for aerobic glycolysis, anti-inflammatory/tissue repair M2 macrophages are more heavily reliant upon oxidative phosphorylation/fatty acid oxidation. The balance between these two types of metabolism is typically disrupted towards the glycolysis dominant type in both rheumatoid arthritis and atherosclerosis; thus contributing to increased inflammation, sustained inflammatory amplification, and exacerbated tissue damage. Metabolic regulators involved in modulating the glycolytic metabolism of macrophages include Pim2 kinase (in rheumatoid arthritis), phosphoglycerate kinase 1, pyruvate dehydrogenase E1 alpha 1 (in rheumatoid arthritis), and granulocyte-macrophage colony stimulating factor (in rheumatoid arthritis). Furthermore, in coronary heart disease, activation of the PI3K/AKT pathway increases the programming of glycolytic metabolism in macrophages and increases plaque inflammation/lesion instability while the oxidative metabolism associated with M2 macrophages results in resolution/plaque stability. Given this context, there is an increasing amount of evidence demonstrating that certain compounds found within traditional Chinese medicines, including berberine, ginsenoside Rb1 and formulae targeted at the HIF-1α/PDK1 axis can be used to re-balance macrophage metabolism to induce a shift away from inflammatory dominance. This review focuses on the dual roles of macrophage metabolic re-programming in rheumatoid arthritis and coronary heart disease, compare common/disease specific signaling components such as HIF-1α, AMPK, and mTORC1 and evaluate the therapeutic potential of traditional Chinese medicine for restoring immunometabolic homeostasis.