In the last decades, the extension of life expectancy and the increased consumption
of foods rich in saturated fats and added sugars have exposed the general population to emerging
health problems.
The prevalence of metabolic syndrome (MS), composed of a cluster of factors as obesity,
dyslipidemia, hyperglycemia, and hypertension, is rapidly increasing in industrialized and developing
countries leading to precocious onset of age-related diseases. Indeed, oxidative
stress, accumulation of advanced glycation endproducts, and a chronic low-grade inflammation
are common features of MS and physiological ageing. In particular, the entire set of MS
factors contributes to the development of an inflammatory status named metaflammation,
which has been associated with activation of early innate immune response through the assembling
of the multiprotein complex inflammasome. The most investigated family of inflammasome
platforms is the NOD-like receptor pyridine containing (NLRP) 3, which is activated
by several exogenous and endogenous stimuli, leading to the sequential cleavage of
caspase-1 and IL-1β, followed by secretion of active IL-1β. We here collect the most recent
findings on NLRP3 activation in MS providing evidence of its central role in disease progression
and organ dysfunction in target tissues of metaflammation, in particular in cardiovascular,
hepatic and renal complications, with a focus on oxidative stress and advanced glycation
endproducts. A wide overview of the most promising strategies for the modulation of NLRP3
activation and related metabolic repercussions is also provided, since the finding of specific
pharmacological tools is an urgent requirement to reduce the social and economic burden of
MS- and elderly-associated diseases.
Potential role of HMG CoA reductase inhibitor on oxidative stress induced by advanced glycation endproducts in vascular smooth muscle cells of diabetic vasculopathy
