Diabetes propels the risk for cardiovascular disease: sweet monocytes becoming aggressive?

Abstract

Diabetes strongly predisposes to cardiovascular disease (CVD), the leading cause of mortality in these patients, as well as in the entire population. Hyperglycemia is an important cardiovascular risk factor as shown by the observation that even transient periods of hyperglycemia, despite return to normoglycemia during follow-up, increase the risk for CVD, a phenomenon termed ‘hyperglycemic memory’. The molecular mechanisms underlying this phenomenon remain largely unknown. As inflammation plays an important role in the pathogenesis of atherosclerosis, we propose that long-term functional reprogramming of monocytes and macrophages, induced by hyperglycemia, plays an important role in the phenomenon of hyperglycemic memory leading to cardiovascular complications in patients with diabetes. In this review, we discuss recent insights showing that innate immune cells possess the capacity to reprogram their function through epigenetically mediated rewiring of gene transcription, a process termed ‘trained immunity’. The long-term reprogramming of monocytes can be induced by microbial as well as metabolic products, and involves a shift in cellular metabolism from oxidative phosphorylation to aerobic glycolysis. We hypothesize that hyperglycemia in diabetes patients induces long-term activation of monocytes and macrophages through similar mechanisms, thereby contributing to plaque development and subsequent macrovascular complications.

The regulatory role of ProBDNF in monocyte function: Implications in Stanford type‐A aortic dissection disease

“…This is because diabetes greatly influence the inflammatory status of peripheral monocytes. 27 In addition, several evidence also revealed that coronary heart disease contributes to the alterations of subtypes and immune functions of monocytes. 28 Thus, our findings suggested that monocytes-derived proBDNF is closely associated with the inflammatory response during the progress of AAD.…”

The role of the interleukin‐1 family in trained immunity

“…The discovery of trained immunity determined a paradigm shift in the field of immunology. As the list of diseases in which trained immunity is suspected to play a role is growing, a better understanding of the underlying mechanisms becomes crucial. Here, we reviewed the available evidence that the IL‐1 family of cytokines and receptors plays an essential role in trained immunity.…”

Epigenetic regulation in monocyte/macrophage: A key player during atherosclerosis

“…The latest study showed that the risk factors facilitated the pathogenesis of atherosclerosis by having impacts on monocyte/macrophage. Diabetes, one of the risks factors for atherosclerosis, contributes to the progression of atherosclerosis by inducing long‐term activation of monocytes and macrophages . LDL, on behalf of the hyperlipidemia environment, promotes monocyte‐to‐macrophage differentiation by inducing human monocytes that express more cell adhesion molecules and cut down the apoptosis of monocytes .…”

“…Diabetes, one of the risks factors for atherosclerosis, contributes to the progression of atherosclerosis by inducing longterm activation of monocytes and macrophages. 28 LDL, on behalf of the hyperlipidemia environment, promotes monocyte-to-macrophage differentiation by inducing human monocytes that express more cell adhesion molecules and cut down the apoptosis of monocytes. 29 It seems that when under a circumstance which is more sweet and greasy, monocytes will be more aggressive and easy to be activated.…”