Microglia are innate immune cells of the brain, and their dysfunction is implicated in the progression of neurodegenerative conditions. Microglia become overly activated and inflammatory with age, likely a reaction to cell damage and dysfunction resulting from mechanisms of aging, as well as to a rising background level of chronic inflammatory signaling characteristic of the aged environment, which the microglia then amplify. Here, researchers discuss how these pro-inflammatory changes in the brain can influence the development of cardiovascular disease outside the brain.
Microglia, commonly known as brain-resident immune cells, are ubiquitously present in the central nervous system (CNS) and participate in the monitoring of the microenvironment. Microglia are abundant within the brain and comprise up to approximately 20% of the total glial cells. Microglia are involved in almost all brain diseases, including neurodegenerative diseases, traumatic brain injury, and mental illness. After activation, microglia can secrete pro-inflammatory and anti-inflammatory mediators and play a broad role during CNS injury.
The autonomic nervous system, which comprises the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS), contributes to the regulation of cardiac function. Sympathetic outflow is controlled by key regions and neural circuits in the CNS. The imbalance between the SNS and PNS, especially the continuous activation of the SNS, is one of the main contributors to pathological cardiac remodeling. However, the upstream regulators of SNS activity remain largely unknown. Recently, studies have shown that microglia may play an important role in regulating SNS activities and cardiovascular function by releasing various substances, including cytokines, chemokines, and growth factors.
Increased neuroinflammation and sympathetic tone contribute to the incidence and maintenance of hypertension. Additionally, after myocardial infarction, microglial activation in the hypothalamus has been observed, and increased levels of pro-inflammatory cytokines in the PVN then activate the hypothalamus-pituitary-adrenal axis, increase the activity of the sympathetic nervous system and contribute to the acute pro-inflammatory response in the myocardium after myocardial infarction. In summary, microglia play an important role in the crosstalk between the CNS and the peripheral nervous system, and interventions targeting microglia may represent promising potential therapies for cardiovascular diseases, including hypertension, myocardial infarction, heart failure, cardiac ischemia/reperfusion and ventricular arrhythmias.