Dysregulation of monocyte biology in metabolic syndrome

Abstract

Metabolic syndrome (MetS), which constitutes a cardio-metabolic risk cluster, is becoming a global epidemic. It is a pro-inflammatory and pro-oxidant state that confers an increased risk of cardiovascular disease and diabetes. MetS is not only characterized by increased circulating biomarkers of inflammation and oxidative stress but also by dysregulation of a pivotal phagocyte, the circulating monocyte. Pertubations manifesting in monocytes of patients with MetS include increased Toll-like receptors, CD40-CD40L dyad, increased ER stress, increased CCR5 and Fc-γ receptors (CD32 and CD64). Additionally, the monocytes demonstrate increase in NADPH oxidase activity and decreased Nrf2, resulting in oxidative damage to biomolecules. Thus the dysregulated monocyte in MetS appears to be a critical cell in the predisposition of MetS patients to diabetes and CVD. Therapeutic strategies targeting monocytes can attenuate this risk and the most compelling data derives from studies with statin therapy.

Keywords::

• inflammation
• metabolic syndrome
• monocytes
• NADPH oxidase
• oxidative stress
• Toll-like receptors

Financial & competing interests disclosures

Studies cited in this review were funded by the NIH, and American Diabetes Association. I Jialal has received support from ADA and NIH grants and S Devaraj has received support from ADA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Metabolic syndrome (MetS) is fast becoming a global epidemic and predisposes to both diabetes and cardiovascular disease.

• Numerous studies support a pivotal role of monocyte dysregulation to the proinflammatory state of MetS.

• Also studies point toward a significant role of monocyte reactive oxygen species such as superoxide anion contributing to the pro-oxidant state of MetS.

• With respect to therapeutic agents tested, statins appear to attenuate the proinflammatory burden of MetS and coupled to their potent low-density lipoprotein-cholesterol-lowering effects, become very attractive candidates.